Process for the preparation of organic bromides

ABSTRACT

The present invention provides a process for the preparation of organic bromides, by a radical bromodecarboxylation of carboxylic acids with a bromoisocyanurate.

FIELD OF THE INVENTION

The present invention provides a process for the preparation of organicbromides, by a radical bromodecarboxylation of carboxylic acids with abromoisocyanurate. The invention further provides a radiation sensitivecomposition comprising a carboxylic acid and bromoisocyanurate whichgenerates organic bromide upon electromagnetic irradiation.

BACKGROUND OF THE INVENTION

Organic bromides are stable organic compounds, which are usedcommercially for many applications, such as pharmaceuticals,agriculture, disinfectants, flame extinguishing agents, and dyes.Organic bromides have found wide use in numerous industrial applicationsas chemical intermediates for the production of other commercial organiccompounds (Ullmann's Encyclopedia of Industrial Chemistry 2012, v. 6,331-358; v. 8, 483-519).

Reaction of benzoic acid with tribromoisocyanuric acid (TBCA) intrifluoroacetic acid gave only 3-bromobenzoic acid—the product ofelectrophilic bromination of aromatic C—H bond (Synlett 2013 v. 24,603-605).

Organic carboxylic acids are widely available and cheap raw materials inorganic synthesis. Therefore, the oxidative decarboxylation of organiccarboxylic acids with concomitant replacement by bromine(bromodecarboxylation) is an extremely useful method for regioselectivesynthesis of organic bromides.

The Hunsdiecker reaction (Tetrahedron 1971, v. 27, 5323) is abromodecarboxylation reaction, which utilizes the treatment of anhydroussilver salt of organic acid with molecular bromine in an inert solvent.This reaction, however, is extremely sensitive to presence of traceamounts of water, which lead to the recovery of unreacted acid. Anotherway to perform the Hunsdiecker reaction is by using a mixture of organiccarboxylic acid and Br₂/HgO (J. Org. Chem. 1965, v. 30, 415) instead ofthe silver salt.

Accordingly, the Hunsdiecker reaction and/or its modifications use heavymetal salts such as those of silver and mercury, therefore thedisadvantages of such procedures for the pharmaceutical industry areobvious.

The Barton halo-de-carboxylation procedure (Barton et al., Tetrahedron1985, v. 41, 3901; 1987, v. 43, 4321) is directed to the conversion oforganic carboxylic acids to the esters of N-hydroxypyridine-2-thione.The thiohydroxamic esters are brominated by BrCCl₃. Thiopyridines areformed in the reaction as co-products.

Additional process for converting organic carboxylic acids to theircorresponding bromides is by treating the carboxylic acid with(diacetoxyiodo)benzene and bromine or LiBr as bromine source(Tetrahedron 2000, v. 56, 2703; Synlett 2011, 1563). However, in thisreaction, it is difficult to separate the desired product fromiodobenzene, which is formed as co-product in the reaction.

A bromodecarboxylation of aromatic carboxylic acids using CuBr₂ as thehalogen sources has been developed by Wu et. al. (Tetrahedron Letters2010, v. 51, 6646) and Liu et. al. (Tetrahedron Letters 2013, v. 54,3079), which also utilize the use of heavy metals in their reactions.

Another example for bromodecarboxylation utilizes the reagent system1205-KBr for bromodecarboxylation of electron-rich arenecarboxylic acids(Synlett 2014, v. 25, 2508). This method, however, is limited topreparation of specific brominated phenol ether derivatives.

N-Bromoamides such as N-bromosuccinimide (Chem. Pharm. Bull. 2002, v.50, 941), 1,3-dibromo-5,5-dimethylhydantoin (Bioorg. Med. Chem. 2008, v.16, 10001; Bioorg. Med. Chem. Lett. 2011, v. 21, 3227; Tetrahedron 2014,v. 70, 318), dibromoisocyanuric acid (Monatsh. Chem. 1968, v. 99, 815;1969, v. 100, 42 & 1977, v. 108, 1067), tribromoisocyanuric acid(Synlett 2013, v. 24, 603), are useful reagents for the electrophilicbromination of aromatic carboxylic acids in the meta-position withrespect to the carboxylic group. However, the use of these reagents inbromo-decarboxylation reactions is rather limited.

For example, reaction of N-bromosuccinimide with arenecarboxylic acids,predominantly electron-rich arenecarboxylic acids, yields bromoarenes(IN803DEL1999; JOC 2009, v. 74, 8874; Tetrahedron Lett. 2007, v. 48,5429). Reaction of 3-aryl acrylic and propiolic acids withN-bromosuccinimides (J. Org. Chem. 2002, v. 67, 7861) andtribromoisocyanuric acid (J. Braz. Chem. Soc. 2013, v. 24, 213) yields2-bromovinyl and 2-bromoethynyl arenes. All of these reactions areheterolytic reactions that do not require initiation with radicalinitiators or UV-visible light irradiation.

The conversion of carboxylic acid R—CO₂H, to their correspondingbromide, R—Br, is therefore a rather difficult transformation. There isa need for the development of new strategies for bromodecarboxylation.

SUMMARY OF THE INVENTION

In one embodiment, this invention is directed to a process for thepreparation of organic bromide of formula (1A) from a carboxylic acid offormula (2A) represented by scheme 1:

said process comprises radical bromodecarboxylation reaction ofcarboxylic acid (2A) with a bromoisocyanurate to yield organic bromide(1A);whereinsaid bromoisocyanurate is tribromoisocyanuric acid, dibromoisocyanuricacid, bromodichloroisocyanuric acid, dibromochloroisocyanuric acid,bromochloroisocyanuric acid, or any combination thereof;A is arene, alkane, cycloalkane or saturated heterocycle;n is an integer of at least 1;m is an integer of at least 0; andeach Q is independently F, Cl, Br, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)OMe,C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl,OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R¹,N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any twovicinal Q substituents are joined to form a 5- or 6-membered substitutedor unsubstituted, saturated or unsaturated carbocyclic or heterocyclicring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl orheterocyclyl, wherein said R¹ is optionally substituted by one or moresubstituents of R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl,cycloalkyl or heterocyclyl;

wherein if either one of R² in (2A) is carboxylic group COOH, then therespective R² in (1A) is Br;

wherein the position of said Br and Q in said structure of formula (1A)correspond to the same position of said COOH and Q, respectively in saidstructure of formula (2A).

In one embodiment, this invention is directed to a process for thepreparation of bromoarene (1B)

from an arenecarboxylic acid (2B),

wherein said process comprises radical bromodecarboxylation reaction ofcarboxylic acid (2B) with a bromoisocyanurate;whereinQ¹, Q², Q³, Q⁴, and Q⁵, are each independently selected from: H, F, Cl,Br, R¹, COOH, acyl, C(O)R¹, C(O)OR¹, C(O)OMe, C(O)Cl, C(O)N(R¹)₂, CN,SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹,S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R², N(R¹)SO₂R¹, N(acyl)₂,N[C(O)R¹]SO₂R¹, N[C(O)R¹]2, CF₃; or any two of Q¹ and Q², Q² and Q³, Q³and Q⁴, or Q⁴ and Q⁵, are joined to form a 5- or 6-membered substitutedor unsubstituted, saturated or unsaturated carbocyclic or heterocyclicring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl orheterocyclyl; wherein R¹ is optionally substituted by one or moresubstituents of R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl,cycloalkyl or heterocyclyl;

wherein if either one of Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (2B) iscarboxylic group COOH, then the respective Q¹, Q², Q³, Q⁴, Q⁵, and/or R²in (1B) is Br.

In one embodiment, this invention is directed to a radiation-sensitivecomposition comprising carboxylic acid of formula (2A)

and bromoisocyanurate which generates organic bromide of formula (1A)

upon electromagnetic irradiation,whereinthe bromoisocyanurate is tribromoisocyanuric acid, dibromoisocyanuricacid, bromodichloroisocyanuric acid, dibromochloroisocyanuric acid,bromochloroisocyanuric acid, or any combination thereof;A is arene, alkane, cycloalkane or saturated heterocycle;n is an integer of at least 1;m is an integer of at least 0;each Q is independently F, Cl, Br, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)Cl,C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹,OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R¹, N(R¹)SO₂R¹,N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two vicinal Qsubstituents are joined to form a 5- or 6-membered substituted orunsubstituted, saturated or unsaturated carbocyclic or heterocyclicring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl orheterocyclyl, wherein R¹ is optionally substituted by one or moresubstituents of R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl,cycloalkyl or heterocyclyl;

wherein if either one of R² in (2A) is a carboxylic group COOH, then therespective R² in (1A) is Br;

wherein the position of said Br and Q in said structure of formula (1A)correspond to the same position of said COOH and Q, respectively in saidstructure of formula (2A).

In one embodiment, this invention is directed to a compositioncomprising an organic bromide of formula (1A) or (1B)

wherein said organic bromide of formula (1A) or (1B) is preparedaccording to the process of this invention.

In one embodiment, the process and composition of this invention furthercomprises an additive. In another embodiment, said additive is Br₂(bromine), a salt comprising bromide or a polybromide anion and anorganic or inorganic cation; or any combination thereof.

In one embodiment, the process of the invention is conducted in thepresence of an organic or an inorganic solvent or combination thereofand the composition of this invention comprises an organic or inorganicsolvent or combination thereof. In another embodiment, the inorganicsolvent is CO₂ or SO₂, or combination thereof. In another embodiment,the organic solvent is CH₃CN, CH₃NO₂, an ester, a hydrocarbon solvent,or halocarbon solvent or combination thereof. In another embodiment, thehydrocarbon solvent is C₆H₆. In another embodiment, the halocarbonsolvent is CH₂Cl₂, Cl(CH₂)₂Cl, CHCl₃, CCl₄, C₆H₅Cl, o-C₆H₄Cl₂, BrCCl₃,CH₂Br₂, CFCl₃, CF₃CCl₃, ClCF₂CFCl₂, BrCF₂CFClBr, CF₃CClBr₂, CF₃CHBrCl,C₆H₅F, C₆H₅CF₃, 4-ClC₆H₄CF₃, 2,4-Cl₂C₆H₃CF₃ or any combination thereof.

In one embodiment, in order to accelerate the radicalbromodecarboxylation reaction the reaction mixture is subjected toelectromagnetic irradiation. In another embodiment, the electromagneticirradiation is microwave, infrared, ultraviolet, or visible lightirradiation or any combination thereof. In another embodiment, theelectromagnetic irradiation is visible light irradiation. In anotherembodiment, the source of said visible light is sunlight, fluorescentlamp, light-emitting diode, incandescent lamp or any combinationthereof.

In one embodiment, the process and composition of this inventioncomprises bromoisocyanurate and a carboxylic acid compound of formula(2A) or (2B). In another embodiment, the molar ratio betweenbromoisocyanurate/(each carboxylic group of the carboxylic acid offormula (2A)) is between 0.1 and 2.

In one embodiment, the process and composition of this inventioncomprises bromoisocyanurate, additive and a carboxylic acid compound offormula (2A) or (2B). In another embodiment, the molar ratio between theadditive/(each carboxylic group of the carboxylic acid of formula (2A))is between 0.1 and 4.

In one embodiment, the bromodecarboxylation reaction is conducted at atemperature of between −20° C. and 150° C. In another embodiment, thebromodecarboxylation reaction is conducted at a temperature of between0° C. and 100° C.

DETAILED DESCRIPTION OF THE PRESENT INVENTION

In the following detailed description, numerous specific details are setforth in order to provide a thorough understanding of the invention.However, it will be understood by those skilled in the art that thepresent invention may be practiced without these specific details. Inother instances, well-known methods, procedures, and components have notbeen described in detail so as not to obscure the present invention.

In recent years, free radical reactions have developed greatly in thegeneral field of organic synthesis. These free radical reactions have anumber of significant advantages relative to the more conventional ionicreactions. First, free radical chain reactions can generally beconducted under neutral conditions. In addition, these reactions areperformed under very mild conditions, which make it possible to avoidinterference of a steric or polar nature occurring with the startingmaterials. Furthermore, this type of reaction is generally notaccompanied by spurious reactions of carbocationic rearrangement orcarbanionic elimination.

The present invention therefore had the object of perfecting a newprocess for the formation of carbon containing free radicals, thefunctionality of which is unmodified relative to the starting materials.The process of the invention consists essentially of a free radicalbromodecarboxylation of organic acids which can be aromatic or aliphaticcarboxylic acid. The mild conditions for carrying out this process haveenabled excellent yields of free radicals to be obtained which retain,in particular, the ether, ester, ketone, and nitro functions of thestarting material.

In one embodiment, this invention is directed to a process for thepreparation of organic bromide of formula (1A) from a carboxylic acid offormula (2A) represented by scheme 1:

said process comprises radical bromodecarboxylation reaction ofcarboxylic acid (2A) with a bromoisocyanurate to yield organic bromide(1A);whereinsaid bromoisocyanurate is tribromoisocyanuric acid, dibromoisocyanuricacid, bromodichloroisocyanuric acid, dibromochloroisocyanuric acid,bromochloroisocyanuric acid, or any combination thereof;A is arene, alkane, cycloalkane or saturated heterocycle;n is an integer of at least 1;m is an integer of at least 0; andeach Q is independently F, Cl, Br, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)Cl,C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹,OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R¹, N(R¹)SO₂R¹,N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two vicinal Qsubstituents are joined to form a 5- or 6-membered substituted orunsubstituted, saturated or unsaturated carbocyclic or heterocyclicring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl orheterocyclyl, wherein said R¹ is optionally substituted by one or moresubstituents of R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl,cycloalkyl or heterocyclyl;

wherein if either one of R² in (2A) is carboxylic group COOH, then therespective R² in (1A) is Br;

wherein the position of said Br and Q in said structure of formula (1A)correspond to the same position of said COOH and Q, respectively in saidstructure of formula (2A).

In one embodiment, this invention is directed to a process for thepreparation of organic bromide of formula (1B) from a carboxylic acid offormula (2B) represented by scheme 2:

said process comprises radical bromodecarboxylation reaction ofcarboxylic acid (2B) with a bromoisocyanurate to yield organic bromide(1B);wherein said bromoisocyanurate is tribromoisocyanuric acid,dibromoisocyanuric acid, bromodichloroisocyanuric acid,dibromochloroisocyanuric acid, bromochloroisocyanuric acid, or anycombination thereof;wherein Q¹, Q², Q³, Q⁴, and Q⁵, are each independently selected from: H,F, Cl, Br, COOH, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)Cl, C(O)N(R¹)₂, CN,SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹,S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R², N(R¹)SO₂R¹, N(acyl)₂,N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two of Q¹ and Q², Q² and Q³, Q³and Q⁴, or Q⁴ and Q⁵, are joined to form a 5- or 6-membered substitutedor unsubstituted, saturated or unsaturated carbocyclic or heterocyclicring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl orheterocyclyl; wherein R¹ is optionally substituted by one or moresubstituents of R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl,cycloalkyl or heterocyclyl;

wherein if either one of Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (2B) iscarboxylic group COOH, then the respective Q¹, Q², Q³, Q⁴, Q⁵, and/or R²in (1B) is Br.

In one embodiment, A of the organic bromide (1A) and of the carboxylicacid (2A) in scheme 1 is arene. In another embodiment, A of the organicbromide (1A) and the carboxylic acid (2A) in scheme 1 is an alkane. Inanother embodiment, A of the organic bromide (1A) and of the carboxylicacid (2A) in scheme 1 is a cycloalkane. In another embodiment, A of theorganic bromide (1A) and of the carboxylic acid (2A) in scheme 1 is asaturated heterocycle.

In one embodiment the A is substituted with one or more substituents Q(in Scheme 1); where each Q is independently F, Cl, Br, R¹, acyl,C(O)R¹, C(O)OR¹, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺,OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl,N(R¹)C(O)R¹, N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; orany two vicinal Q substituents are joined to form a 5- or 6-memberedsubstituted or unsubstituted, saturated or unsaturated carbocyclic orheterocyclic ring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl orheterocyclyl, wherein R¹ is optionally substituted by one or moresubstituents of R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl,cycloalkyl or heterocyclyl.

In another embodiment, Q does not comprise electron donatingsubstituents in the aromatic ring. Examples for electron donatingsubstitutions include but not limited to: OH, NH₂, NH-alkyl, N(alkyl)₂.

In another embodiment, Q is at least one of NO₂, Cl, F, Br, CN, C(O)OMe,or CF₃.

In another embodiment, each Q is independently Cl. In anotherembodiment, each Q is independently F. In another embodiment, each Q isindependently Br. In another embodiment, each Q is independently CN. Inanother embodiment, each Q is independently CF₃. In another embodiment,each Q is independently CCl₃. In another embodiment, each Q isindependently acyl group. In another embodiment, each Q is independentlySO₃R¹. In another embodiment, each Q is independently SO₂R¹. In anotherembodiment, each Q is independently COR¹. In another embodiment, each Qis independently C(O)OR¹. In another embodiment, each Q is independentlyC(O)OMe. In another embodiment, each Q is independently COCl. In anotherembodiment, each Q is independently amide. In another embodiment, each Qis independently C(O)N(R¹)₂. In another embodiment, each Q isindependently OCF₃. In another embodiment, each Q is independently R¹.In another embodiment, each Q is independently alkyl. In anotherembodiment, each Q is independently t-Bu. In another embodiment, each Qis independently cycloalkyl. In another embodiment, each Q isindependently heterocyclyl. In another embodiment, each Q isindependently OR¹. In another embodiment, each Q is independently OMe.In another embodiment, each Q is independently SR¹. In anotherembodiment, each Q is independently SMe. In another embodiment, each Qis independently acetyl. In another embodiment, each Q is independentlybenzoyl. In another embodiment, each Q is independently mesyl. Inanother embodiment, each Q is independently tosyl. In anotherembodiment, each Q is independently NO₂. In another embodiment, each Qis independently N(R¹)₃ ⁺. In another embodiment, each Q isindependently O-acyl. In another embodiment, each Q is independentlyOC(O)R¹. In another embodiment, each Q is independently acetoxy. Inanother embodiment, each Q is independently OSO₂R¹. In anotherembodiment, each Q is independently mesyloxy. In another embodiment,each Q is independently tosyloxy. In another embodiment, each Q isindependently S-acyl. In another embodiment, each Q is independentlySC(O)R¹. In another embodiment, each Q is independently N(R¹)acyl. Inanother embodiment, each Q is independently N(R¹)C(O)R¹. In anotherembodiment, each Q is independently N(R¹)SO₂R¹. In another embodiment,each Q is independently N(acyl)₂. In another embodiment, each Q isindependently N[C(O)R¹]SO₂R¹. In another embodiment, each Q isindependently saccharinyl. In another embodiment, each Q isindependently N[C(O)R¹]₂. In another embodiment, each Q is independentlyphthalimido. In another embodiment, each Q is independently aryl. Inanother embodiment, each Q is independently C₆H₅. In another embodiment,each Q is independently C₆F₅. In another embodiment, two vicinal Qsubstituents are joined to form a 5- or 6-membered substituted orunsubstituted, saturated or unsaturated heterocyclic ring. In anotherembodiment, two vicinal Q substituents are joined to formdihydrofuran-2,5-dione. In another embodiment, two vicinal Qsubstituents are joined to form pyrrolidine-2,5-dione. In anotherembodiment, if m>1 then Q substituents are the same. In anotherembodiment, if m>1 then Q substituents are different.

In one embodiment, A of the organic bromide (1A) and of the carboxylicacid (2A) in scheme 1 is a benzene. In another embodiment, A iscycloalkane. In another embodiment, A is a saturated heterocycle.

In another embodiment A of the organic bromide (1A) and of thecarboxylic acid (2A) in scheme 1 is an alkane. In another embodiment,the alkane chain is linear. In another embodiment, the alkane chain isbranched.

In one embodiment, the carboxylic acid (2A) in scheme 1 is notECH(Z)—COOH, wherein E is acyl, CO₂Z′, SO₂Z′, S(Z′)₂ ⁺, or N(Z′)₃+ and Zand Z′ are each independently a hydrogen, alkyl or an aryl. In anotherembodiment, the carboxylic acid (2A) in scheme 1 is not ZCH═CH—COOH orZC≡C—COOH, where Z is either a hydrogen, alkyl or an aryl, the lattertwo are optionally substituted. In another embodiment, the A in scheme 1is not unsaturated heterocycle. In another embodiment, the A in scheme 1is not alkene or alkyne. In another embodiment, the A in scheme 1 is notcycloalkene or cycloalkyne. In another embodiment, the Q in scheme 1 isnot OH, NH₂, NHR, or NR₂ group.

In another embodiment, at least one of Q¹, Q², Q³, Q⁴, and/or Q⁵ is F,Cl, Br, CF₃, CCl₃, CN, COOH, C(O)OMe, NO₂, phthalimide, OCF₃, and/or anytwo of Q¹ and Q², Q² and Q³, Q³ and Q⁴, or Q⁴ and Q⁵, are joined to forma dihydrofuran-2,5-dione or pyrrolidine-2,5-dione ring.

In another embodiment, at least one of Q¹, Q², Q³, Q⁴, and Q⁵ is NO₂. Inanother embodiment, at least one of Q¹, Q², Q³, Q⁴, and Q⁵ is CF₃. Inanother embodiment, at least one of Q¹, Q², Q³, Q⁴, and Q⁵ is CN. Inanother embodiment, at least one of Q¹, Q², Q³, Q⁴, and Q⁵ is Cl. Inanother embodiment, at least one of Q¹, Q², Q³, Q⁴, and Q⁵ is F. Inanother embodiment, at least one of Q¹, Q², Q³, Q⁴, and Q⁵ is Br. Inanother embodiment, at least one of Q¹, Q², Q³, Q⁴, and Q⁵ isphthalimide. In another embodiment, at least one of Q¹, Q², Q³, Q⁴, andQ⁵ is C(O)OMe.

In one embodiment, Q¹ of formula (1B) and (2B) in scheme 2 is F. Inanother embodiment, Q¹ is H. In another embodiment, Q¹ is CF₃. Inanother embodiment, Q¹ is Cl. In another embodiment, Q¹ is Br. Inanother embodiment, Q¹ is NO₂. In another embodiment, Q¹ is CO₂Me. Inanother embodiment, Q¹ is phthalimide.

In one embodiment, Q² of formula (1B) and (2B) in scheme 2 is H. Inanother embodiment, Q² is F. In another embodiment, Q² is CF₃. Inanother embodiment, Q² is Cl. In another embodiment, Q² is Br. Inanother embodiment, Q² is CN. In another embodiment, Q² is NO₂. Inanother embodiment, Q² is CO₂Me. In another embodiment, Q² is COOH.

In one embodiment, Q³ of formula (1B) and (2B) in scheme 2 is H. Inanother embodiment, Q³ is CN. In another embodiment, Q³ is Cl. Inanother embodiment, Q³ is Br. In another embodiment, Q³ is F. In anotherembodiment, Q³ is CF₃. In another embodiment, Q³ is NO₂. In anotherembodiment, Q³ is CO₂Me. In another embodiment, Q³ is COOH.

In one embodiment, Q⁴ of formula (1B) and (2B) in scheme 2 is H. Inanother embodiment, Q⁴ is F. In another embodiment, Q⁴ is CF₃. Inanother embodiment, Q⁴ is CN. In another embodiment, Q⁴ is Cl. Inanother embodiment, Q⁴ is NO₂.

In one embodiment, Q⁵ of formula (1B) and (2B) in scheme 2 is H. Inanother embodiment, Q⁵ is F. In another embodiment, Q⁵ is CF₃. Inanother embodiment, Q⁵ is CN. In another embodiment, Q⁵ is Cl.

In one embodiment, Q³ and Q⁴ of formula (1B) and (2B) in scheme 2 arejoined to form a 5- or 6-membered substituted or unsubstituted,saturated or unsaturated heterocyclic ring. In another embodiment, theheterocyclic ring is dihydrofuran-2,5-dione. In another embodiment, theheterocyclic ring is pyrrolidine-2,5-dione. In another embodiment, theheterocyclic ring is substituted with an alkyl. In another embodiment,the alkyl is t-Bu.

In one embodiment, m of scheme 1 and of compounds (1A) and (2A) is aninteger number greater than or equal to 0. In another embodiment, m is0. In another embodiment, m is 1. In another embodiment, m is 2. Inanother embodiment, m is 3. In another embodiment, if m>1 than Q can bedifferent or the same.

In one embodiment, n of compounds (1A), (2A) in scheme 1 is an integernumber greater than or equal to 1. In another embodiment, n is between 1and 5. In another embodiment, n is between 1 and 3. In anotherembodiment, n is 1 or 2. In another embodiment, n is 1. In anotherembodiment, n is 2. In another embodiment, n is 3.

In one embodiment, this invention is directed to a process for thepreparation of organic bromide from its corresponding carboxylic acid,said process comprises a radical bromodecarboxylation reaction of thecarboxylic acid with a bromoisocyanurate, wherein said carboxylic acidis selected from the carboxylic acids listed in Tables 4, 5, 6 and 11below.

According to this invention, the term “bromoisocyanurate” refers totribromoisocyanuric acid, dibromoisocyanuric acid,bromodichloroisocyanuric acid, dibromochloroisocyanuric acid,bromochloroisocyanuric acid, or any combination thereof. In oneembodiment, the bromoisocyanurate reagent used in the process of theinvention is freshly prepared according to known procedures [Journal ofthe Swimming Pool and Spa Industry 2004, v. 5, 16]. In anotherembodiment, tribromoisocyanuric acid, dibromoisocyanuric acid,bromodichloroisocyanuric acid, dibromochloroisocyanuric acid, and/orbromochloroisocyanuric acid are stable. In another embodiment,dibromoisocyanuric acid is commercially available.

In one embodiment, the process of this invention, represented by schemes1 and 2, has a radical mechanism. In another embodiment all factors thatpromote radical reaction may stimulate the process of this invention.Factors that promote radical reaction: heating, electromagneticirradiation, addition of radical initiators

In one embodiment, the reaction mixture of the process of this inventionand the composition of this invention further comprises an additive. Inanother embodiment, the additive is bromine, a salt comprising bromideor a polybromide anion and an organic or inorganic cation; or anycombination thereof. In another embodiment, the cation is a substitutedor unsubstituted onium ion. The term “onium” refers in one embodiment tocations (with their counter-ions) derived by addition of a hydron to amononuclear parent hydride of the nitrogen, chalcogen and halogenfamilies. Non limiting examples of oniums include [NH₄]⁺ ammonium,[OH₃]⁺ oxonium, [PH₄]⁺ phosphonium, [SH₃]⁺ sulfonium, [AsH₄]⁺ arsonium,[SeH₃]⁺ selenonium, [BrH₂]⁺ bromonium, [SbH₄]⁺) stibonium, [TeH₃]⁺)telluronium, [IH₂]⁺ iodonium, [BiH₄]⁺ bismuthonium.

Substituted oniums refers to substitution of the above parent ions byunivalent groups or by two or three free valencies. E.g. [SMe₃]⁺trimethylsulfonium (a tertiary sulfonium ion), [MePPh₃]⁺methyltriphethylphosphonium (a quaternary phosphonium ion), [HNEt₃]⁺triethylammonium (a tertiary ammonium ion), [NPr₄]⁺ tetrapropylammonium(a quaternary ammonium ion), [R₂C═NR₂]⁺ iminium ions.

In one embodiment, the term “inorganic cation” used herein refers toalkali or alkaline earth metal cations, transition metal cation, orunsubstituted onium cation. In another embodiment, the inorganic cationis Li⁺. In another embodiment, the inorganic cation is Na⁺. In anotherembodiment, the inorganic cation is K⁺. In another embodiment, theinorganic cation is Rb⁺. In another embodiment, the inorganic cation isCs⁺. In another embodiment, the inorganic cation is Zn²⁺. In anotherembodiment, the inorganic cation is Cu²⁺. In another embodiment, theinorganic cation is ammonium cation [Na₄]⁺.

In one embodiment, the term “organic cation” used herein refers tosubstituted onium cation. In another embodiment, the substituted oniumcation is substituted ammonium cation, substituted phosphonium cation,substituted oxonium cation, substituted sulfonium cation, substitutedarsonium cation, substituted selenonium cation, substituted telluroniumcation, substituted iodonium cation, any other known onium cation, orany combination thereof. In another embodiment, the substituted ammoniumcation is the substituted or unsubstituted guanidinium cation,substituted or unsubstituted pyridinium cation, substituted orunsubstituted amidinium cation, substituted or unsubstituted quaternaryammonium cation [NR¹ ₄]⁺, substituted or unsubstituted tertiary ammoniumcation [HNR¹ ₃]⁺. In another embodiment, the substituted phosphoniumcation is substituted or unsubstituted quaternary phosphonium cation[PR¹ ₄]⁺, wherein R¹ is alkyl, aryl, cycloalkyl, heterocyclyl, or anycombination thereof. In another embodiment, the quaternary ammoniumcation [NR¹ ₄]⁺ is tetraalkylammonium, trialkylarylammonium,dialkyldiarylammonium, trialkylbenzylammonium, or any combinationthereof. In another embodiment, non-limiting examples of the quaternaryammonium cation [NR¹ ₄]⁺ include tetrametylammonium, tetraethylammonium,tetrabutylammonium, tetraoctylammonium, trimethyloctylammonium,cetyltrimethylammonium, or any combination thereof. In anotherembodiment, the quaternary phosphonium cation [PR¹ ₄]⁺ istetraalkylphosphonium, alkyltriarylphosphonium,benzyltriarylphosphonium, benzyltrialkylphosphonium, or any combinationthereof. In another embodiment, non-limiting examples of the quaternaryphosphonium cation [PR¹ ₄]⁺ include tetraphenylphosphonium,benzyltriphenylphosphonium, tetrabutylphosphonium,methyltriphenylphosphonium, benzyltributylphosphonium cation or anycombination thereof. In another embodiment, the substituted sulfoniumcation is substituted or unsubstituted tertiary sulfonium cation,substituted or unsubstituted sulfoxonium, thiopyrylium or thiuroniumion; or any combination thereof. In another embodiment the substitutedoxonium cation is substituted or unsubstituted tertiary oxonium cation,substituted or unsubstituted pyrylium cation; or any combinationthereof.

In another embodiment, substituted cations as referred herein aresubstituted with halide, nitrile, nitro, alkyl, aryl, cycloalkyl,heterocyclyl, amide, carboxylic acid, acyl or any combination thereof.

In one embodiment, the term “polybromide anion” used herein refers to amolecule or ion containing three or more bromine atoms or to an ion offormula [Br_(p)]^(q−), where p is an integer of at least 3 and q is aninteger of at least 1 and not more than p/2. In another embodiment, p isan integer between 3-24 and q is 1 or 2. In another embodiment p is 3,5, 7, 9, 11 or 13 and q is 1. In another embodiment p is 4, 8, 20 or 24and q is 2.

In another embodiment, the additive is Br₂, [NPr₄]Br, [NPr₄]Br₃,[NPr₄]Br₉, or any combination thereof.

An “alkyl” refers, in one embodiment, to a univalent groups derived fromalkanes by removal of a hydrogen atom from any carbon atom:C_(n)H_(2n+1)—. In one embodiment, the alkyl group has 1-20 carbons.Examples for alkyls include but are not limited to: methyl, ethyl,propyl, isopropyl, butyl, isobutyl, s-butyl, tert-butyl, pentyl,neopentyl, octyl, isooctyl and the like

The term “alkane” refers to acyclic branched or unbranched hydrocarbonshaving the general formula C_(n)H_(2n+2), and therefore consistingentirely of hydrogen atoms and saturated carbon atoms. Examples ofalkane include: methane, ethane, propane, n-butane, isobutane,n-pentane, neopentane, n-octane, isooctane and the like.

An “arene” refers to monocyclic and polycyclic aromatic hydrocarbons.Nonlimiting examples of arenes are benzene, biphenyl, naphthalene,anthracene, and the like.

An “aryl” group refers, to univalent groups derived from arenes byremoval of a hydrogen atom from a ring carbon atom. Nonlimiting examplesof aryl groups are phenyl, naphthyl, antracenyl, phenanthryl, and thelike.

A “cycloalkyl” refers to univalent groups derived from cycloalkanes byremoval of a hydrogen atom from a ring carbon atom Non limiting examplesof cycloalkyl include: cyclobutyl, norbornyl, cyclopentyl andcyclohexyl.

A “cycloalkane” refers to saturated mono- or polycyclic hydrocarbons. Ageneral chemical formula for cycloalkanes would be C_(n)H_(2(n+1-g))where n=number of C atoms and g=number of rings in the molecule.

A “heterocyclyl” refers to univalent groups formed by removing ahydrogen atom from any ring atom of a mono or polycyclic heterocycliccompound.

A “heterocycle” refers to a mono- or poly-cyclic heterocyclic compoundconsisting of carbon, hydrogen and at least one of nitrogen, sulfur,oxygen, phosphorous or combination thereof in one of the rings. In oneembodiment, the heterocyclic compound consists 2-7 fused rings. Nonlimiting examples of monocyclic saturated heterocyclic compounds areaziridine, oxirane, thiirane, azetidine, oxetane, thietane, pyrrolidine,tetrahydrofurane, thiolane, pyperidine, oxane, thiane, azepane, oxepane,thiepane, imidazolidine, oxazolidine, thiazolidine, dioxolane,piperazine, morpholine, dioxane, homopiperazine. Non limiting examplesof saturated bicyclic heterocyclic compounds are quinuclidine,7-oxanorbornane, 7-thiabicyclo[2.2.1]heptane,3-oxabicyclo[3.1.1]heptane, 3-azabicyclo[3.1.1]heptane, octahydroindole,octahydro-2-benzofuran.

An “amide” refers, in one embodiment, to a derivative of oxoacid inwhich an acidic hydroxyl group has been replaced by an amino orsubstituted amino group. Compounds having one or two acyl groups on agiven nitrogen are generically included and may be designated as primaryand secondary amides, respectively.

An “acyl” group is formed by removing one or more hydroxyl groups fromoxoacids, and replacement analogues of such acyl groups. E.g. —C(═O)R,—C(═O)OR, —C(═O)NR₂, —C≡N, —S(═O)₂R, —S(═O)₂OR, —NO₂. Non limitingexamples of the acyl groups include acetyl —C(O)Me, benzoyl —C(O)Ph,C(O)OMe, —C(═O)Cl, mesyl MeSO₂—, tosyl 4-MeC₆H₄SO₂—,

A “carboxylic acid” refers, in one embodiment, to oxoacids having thestructure RC(═O)OH.

In another embodiment, the bromodecarboxylation reaction represented byschemes 1 and 2 is conducted at room temperature. In another embodiment,the reaction is conducted under cooling. In another embodiment, thebromodecarboxylation reaction is initiated thermally. In anotherembodiment, the bromodecarboxylation reaction is further subjected toheat. In another embodiment, the bromodecarboxylation reaction isconducted at a temperature of between −20° C. and 150° C. In anotherembodiment, said process is conducted at a temperature of between about0° C. and about 100° C.

In another embodiment, the process of this invention further comprisingthe use of radical initiator in the reaction. In another embodiment, theradical initiator is an azo compound or organic peroxide. In anotherembodiment, the azo compound is azobisisobutyronitrile (AIBN) or1,1′-azobis(cyclohexanecarbonitrile) (ABCN). In another embodiment, theorganic peroxide is benzoyl peroxide.

In another embodiment, the bromoarene of formula (1A) and/or (1B) isprepared according to process described in Examples 3-11.

In one embodiment, the process of this invention, represented by schemes1 and 2, is conducted under electromagnetic irradiation. In anotherembodiment, the electromagnetic radiation is visible light, infraredradiation, ultraviolet radiation, microwave radiation or any combinationthereof.

In another embodiment, the source of the visible light is sunlight,fluorescent lamp, light-emitting diode, incandescent lamp or anycombination thereof.

The term “irradiation” refers in one embodiment to the energy that isirradiated or transmitted in the form of rays or waves or particles.Electromagnetic irradiation refers to radiation consisting of waves ofenergy associated with electric and magnetic fields resulting from theacceleration of an electric charge. Ultrasound refers to cyclicmechanical vibrations with a frequency greater than 20 kilohertz (20,000hertz). Ultraviolet irradiation refers to electromagnetic radiation withwavelengths 100 to 400 nm. Visible irradiation (light, visible light)refers to electromagnetic irradiation with wavelengths 400 to 780 nm.Infrared irradiation refers to electromagnetic irradiation withwavelengths 780 to 20000 nm. Microwave irradiation refers toelectromagnetic irradiation with wavelengths 2 to 1000 mm.

Devices serving as a source of the electromagnetic irradiation include amercury lamp, a xenon lamp, a carbon arc lamp, an incandescent lamp, atungsten lamp, a fluorescent lamp, light-emitting diode, and sunlight,and the like.

Tungsten lamp refers to incandescent lamp that generates light bypassing an electric current through a thin filament wire (usually ofwolfram) until it is extremely hot. The lamps are often filled by ahalogen gas such as iodine and bromine that allow filaments to work athigher temperatures and higher efficiencies.

Light-emitting diode (LED) refers to a semiconductor (often acombination of gallium, arsenic, and phosphorous or gallium andnitrogen) containing an n region (where electrons are more numerous thanpositive charges) separated from a p region (where positive charges aremore numerous than negative charges). Upon application of a voltage,charges move and emission of ultraviolet, visible, or infrared radiationis produced each time a charge recombination takes place. Although anLED emits incoherent monochromatic light, normally a very narrowfrequency range is obtained.

In another embodiment, the process is conducted in the presence of anorganic or an inorganic solvent or combination thereof and thecomposition of this invention comprises an organic or an inorganicsolvent or combination thereof. In another embodiment, the organicsolvent is CH₃CN, CH₃NO₂, ester, a hydrocarbon solvent, or halocarbonsolvent or combination thereof. In another embodiment the halocarbonsolvent is CH₂Cl₂, Cl(CH₂)₂Cl, CHCl₃, CCl₄, C₆H₅Cl, o-C₆H₄Cl₂, BrCCl₃,CH₂Br₂, CFCl₃, CF₃CCl₃, ClCF₂CFCl₂, BrCF₂CFClBr, CF₃CClBr₂, CF₃CHBrCl,C₆H₅F, C₆H₅CF₃, 4-ClC₆H₄CF₃, 2,4-Cl₂C₆H₃CF₃ or any combination thereof.In another embodiment, the solvent is CH₂Cl₂ or BrCCl₃. In anotherembodiment, the solvent is a polar solvent. In another embodiment, thesolvent is a nonpolar solvent. In another embodiment, the solvent is ahydrocarbon. In another embodiment, the solvent is benzene C₆H₆ (PhH).In another embodiment, the solvent is acetonitrile CH₃CN (MeCN). Inanother embodiment, the solvent is ethyl acetate EtOAc. In anotherembodiment, the solvent is halocarbon. In another embodiment, thesolvent is carbon tetrachloride CCl₄. In another embodiment, the solventis chloroform CHCl₃. In another embodiment, the solvent isbromotrichloromethane BrCCl₃. In another embodiment, the solvent isdibromomethane CH₂Br₂. In another embodiment, the solvent istrichlorofluoromethane CFCl₃. In another embodiment, the solvent is1,1,1-trichlorotrifluoroethane CF₃CCl₃. In another embodiment, thesolvent is 1,1,2-trichlorotrifluoroethane ClCF₂CFCl₂. In anotherembodiment, the solvent is 1,2-dibromo-1-chlorotrifluoroethaneBrCF₂CFClBr. In another embodiment, the solvent is1,1-dibromo-1-chlorotrifluoroethane CF₃CClBr₂. In another embodiment,the solvent is 2-bromo-2-chloro-1,1,1-trifluoroethane CF₃CHBrCl(halothane). In another embodiment, the solvent is fluorobenzene C₆H₅F(PhF). In another embodiment, the solvent is chlorobenzene C₆H₅Cl(PhCl). In another embodiment, the solvent is benzotrifluoride C₆H₅CF₃(PhCF₃). In another embodiment, the solvent is p-chlorobenzotrifluoride4-ClC₆H₄CF₃. In another embodiment, the solvent is 1,2-dichloroethaneCl(CH₂)₂Cl (DCE). In another embodiment, the solvent isortho-dichlorobenzene o-C₆H₄Cl₂. In another embodiment, the solvent isdichloromethane CH₂Cl₂ (DCM). In another embodiment, the solvent is2,4-dichlorobenzotrifluoride 2,4-Cl₂C₆H₃CF₃. In another embodiment,bromodecarboxylation process is preferably conducted in a halocarbonsolvent. In another embodiment, bromodecarboxylation process ispreferably conducted in a BrCCl₃, CH₂Cl₂, CH₂Br₂, CF₃CHBrCl or anycombination thereof.

The term “hydrocarbon solvent” refers to any solvent consisting of thecarbon and hydrogen elements. Non limiting examples of hydrocarbonsolvents are cyclohexane, heptane, pentane, hexane, or benzene C₆H₆.

The term “halocarbon solvent” refers to any solvent wherein one or moreof the carbons are covalently linked to one or more halogens (fluorine,chlorine, or bromine). Non limiting examples of halocarbon solvents arechloroform CHCl₃, dichloromethane CH₂Cl₂ (DCM), bromotrichloromethaneBrCCl₃, chlorobenzene C₆H₅Cl (PhCl), ortho-dichlorobenzene o-C₆H₄Cl₂,1,2-dichloroethane Cl(CH₂)₂Cl (DCE), carbon tetrachloride CCl₄,1,3-dichloropropane Cl(CH₂)₃Cl, 1,1,2,2-tertrachlorodifluoroethaneFCCl₂CCl₂F, 1,1,2-trichloroethane CHCl₂CH₂Cl, bromobenzene C₆H₅Br,1,1,2-trichlorotrifluoroethane ClCF₂CFCl₂, dibromomethane CH₂Br₂,2-bromo-2-chloro-1,1,1-trifluoroethane CF₃CHBrCl (halothane),1,2-dibromoethane Br(CH₂)₂Br, benzotrifluoride C₆H₅CF₃ (PhCF₃),2,4-dichlorobenzotrifluoride 2,4-Cl₂C₆H₃CF₃.

In one embodiment, following the formation of organic bromide, or thecompound of formula (1A) or (1B) the organic bromide is isolated fromthe reaction mixture by filtration, washing, chromatography,crystallization or any combination thereof. In another embodiment thebromo compound is isolated from the reaction mixture by filtrationfollowed by a washing step. In another embodiment the washing stepcomprises washing with an aqueous reducing agent followed by washingwith an aqueous base. In another embodiment the washing step compriseswashing with an aqueous base followed by washing with an aqueousreducing agent. In another embodiment, the washing step compriseswashing with an aqueous reducing agent and a base.

In one embodiment the organic bromide is isolated from the reactionmixture by a washing step.

In another embodiment, the washing step comprises treating of thereaction mixture with reducing agent, wherein excess of thebromoisocyanurate is converted to cyanuric acid insoluble in non-polarorganic solvents, and thereby can be removed from the organic phase. Inanother embodiment, an aqueous reducing agent refers to an aqueoussolution comprising a reducing agent. Non limiting examples of reducingagents are Na₂SO₃, NaHSO₃, Na₂S₂O₃, NaBH₄/NaOH or combination thereof.In another embodiment the reducing agent is added at a concentration ofbetween 1-10% w/w to the water to obtain an aqueous reducing agentsolution.

In one embodiment, the process of this invention directed tobromodecarboxylation comprising a washing step with an aqueous reducingagent. In another embodiment, following the washing step a potassiumiodide starch paper test is performed to identify traces of thebromoisocyanurate. “A potassium iodide starch paper test” (SPT) refersto a starch iodide test paper that has been wetted with aqueous aceticacid; 1:1; v/v]. In another embodiment, if the test is positive, anadditional aqueous reducing agent is added to the reaction mixture.

In another embodiment the washing step comprises washing the productwith a mild aqueous base wherein the unreacted carboxylic acid isremoved from the organic phase by washing with an aqueous base. Inanother embodiment, the carboxylic acid is recovered by acidifying theaqueous phase. In another embodiment, an aqueous base refers to anaqueous solution comprising a base. Non limiting examples of a base isNaHCO₃, NaOH, Na₂CO₃, KOH, Na₂SO₃ or combination thereof. In anotherembodiment the base is added at a concentration of between 1-10% w/w tothe water to obtain an aqueous base solution.

In another embodiment, the washing step with an aqueous reducing agentis conducted before the washing step with the aqueous base. In anotherembodiment, the washing step with the aqueous base is conducted beforethe washing step with the aqueous reducing agent. In another embodiment,the washing step comprises washing with an aqueous reducing agent and abase.

Such a combination of an aqueous reducing agent and a base includesNa₂SO₃ and NaBH₄/NaOH which are basic reducing agents that combineproperties of reducing agent and a base.

In another embodiment, the washing steps of this invention are conductedusing the organic solvent of the reaction mixture as the organic phase.In another embodiment, the washing step with the aqueous base and thewashing step with the aqueous reducing agent are independently performedusing a) the organic solvent of the reaction mixture, b) a mixture oforganic solvents, or c) a different organic solvent, as the organicphase. Non limiting examples of organic solvents used as an organicphase in the washing step are hydrocarbon solvent, halocarbon solvent,or esters such as cyclohexane, heptane, hexane, pentane, benzene,toluene, chlorobenzene, 1,2-dichloroethane, carbon tetrachloride,1,3-dichloropropane, 1,1,2,2-tertrachlorodifluoroethane,1,1,2-trichloroethane, trichloroethylene, perchloroethylene,dichloromethane, chloroform, ethyl acetate or butyl acetate.

In one embodiment, following the washing step, the aqueous phase istreated with an acid or an aqueous acid solution to precipitate solidcyanuric acid.

In one embodiment, the organic bromide product of thebromodecarboxylation reaction is soluble in organic phase and notsoluble in the aqueous phase. In another embodiment, the crude organicbromide is isolated from reaction mixture by standard organic solventextractive work-up.

In one embodiment, removing the solvent from the organic phase gives thecrude desired bromide product as the residue. In another embodiment, theresidue is the pure desired bromide product. In another embodiment, thebromide is purified by crystallization, rectification or chromatographyof the residue.

In another embodiment the isolation and purification further comprises adrying step. In another embodiment the purification further compriseschromatography.

In one embodiment, the process of this invention provides a process forthe preparation of pure organic bromide.

In another embodiment, the “pure bromide” refers to 92% or more purity.In another embodiment, the “pure bromide” refers to about 95% or morepurity. In another embodiment, the “pure bromide” refers to about 90% ormore purity. In another embodiment, the “pure bromide” refers to about85% or more purity. In another embodiment, the “pure bromide” refers toabout 99% or more purity. In another embodiment, the “pure bromide”refers to about 98% or more purity. In another embodiment, the “purebromide” refers to about 97% or more purity.

In one embodiment, this invention is directed to organic bromidecompound represented by the formula (1A) or (1B) having purity of about99% or more, prepared according to the process of this invention. Inanother embodiment, this invention is directed to organic bromidecompound represented by the formula (1A) or (1B) having purity of about98% or more prepared according to the process of this invention. Inanother embodiment, this invention is directed to organic bromidecompound represented by the formula (1A) or (1B) having purity of about90% or more, prepared according to the process of this invention. Inanother embodiment, this invention is directed to organic bromidecompound represented by the formula (1A) or (1B) having purity of about95% or more, prepared according to the process of this invention. Inanother embodiment, this invention is directed to organic bromidecompound represented by the formula (1A) or (1B) having purity of about85% or more, prepared according to the process of this invention. Inanother embodiment, this invention is directed to organic bromidecompound represented by the formula (1A) or (1B) having purity of about97% or more, prepared according to the process of this invention.

In one embodiment, the process of this invention, represented by schemes1 and 2, provides a yield of 60% or more. In another embodiment, theprocess of this invention provides a yield of 70% or more. In anotherembodiment, the process of this invention provides a yield of 80% ormore. In another embodiment, the process of this invention provides ayield of 85% or more. In another embodiment, the process of thisinvention provides a yield of 90% or more. In another embodiment, theprocess of this invention provides a yield of 95% or more.

In one embodiment, this invention is directed to a process comprisingreacting carboxylic acid of formula (2A) or (2B) with bromoisocyanurateand an additive in a certain molar ratio. In another embodiment, thecarboxylic acid compounds (2A) or (2B) can have more than one carboxylicacid groups.

In one embodiment the bromoisocyanurate: (each carboxylic group of thecarboxylic acid of formula (2A)) molar ratio is between 0.1 and 2. Inanother embodiment the bromoisocyanurate: (each carboxylic group of thecarboxylic acid of formula (2A)) molar ratio is between 1 and 2. Inanother embodiment the bromoisocyanurate: (each carboxylic group of thecarboxylic acid of formula (2A)) molar ratio is between 0.1 and 1. Inanother embodiment the bromoisocyanurate: (each carboxylic group of thecarboxylic acid of formula (2A)) molar ratio is 1. In another embodimentthe bromoisocyanurate: (each carboxylic group of the carboxylic acid offormula (2A)) molar ratio is between 1 and 1.5.

In one embodiment, the reaction mixture of the process according to thisinvention, further comprises an additive. In another embodiment, theadditive: (each carboxylic group of the carboxylic acid of formula (2A))molar ration is between 0.1 and 4. In another embodiment, additive:(each carboxylic group of the carboxylic acid of formula (2A)) molarration is between 1 and 4. In another embodiment, the additive: ((eachcarboxylic group of the carboxylic acid of formula (2A)) molar ration isbetween 0.1 and 2. In another embodiment, the additive: (each carboxylicgroup of the carboxylic acid of formula (2A)) molar ration is between0.1 and 1. In another embodiment the additive: (each carboxylic group ofthe carboxylic acid of formula (2A)) molar ration is between 1 and 2. Inanother embodiment the additive: (each carboxylic group of thecarboxylic acid of formula (2A)) molar ration is between 1 and 3.

In one embodiment, this invention is directed to a radiation-sensitivecomposition comprising carboxylic acid of formula (2A)

and bromoisocyanurate which generates organic bromide of formula (1A)

upon electromagnetic irradiation,whereinthe bromoisocyanurate is tribromoisocyanuric acid, dibromoisocyanuricacid, bromodichloroisocyanuric acid, dibromochloroisocyanuric acid,bromochloroisocyanuric acid, or any combination thereof;A is arene, alkane, cycloalkane or saturated heterocycle;n is an integer of at least 1;m is an integer of at least 0;each Q is independently F, Cl, Br, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)Cl,C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹,OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R¹, N(R¹)SO₂R¹,N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two vicinal Qsubstituents are joined to form a 5- or 6-membered substituted orunsubstituted, saturated or unsaturated carbocyclic or heterocyclicring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl orheterocyclyl, wherein R¹ is optionally substituted by one or moresubstituents of R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl,cycloalkyl or heterocyclyl;

wherein if either one of R² in (2A) is a carboxylic group COOH, then therespective R² in (1A) is Br;

wherein said position of Br and Q in said structure of formula (1A)correspond to the same position of said COOH and Q, respectively in saidstructure of formula (2A)

In another embodiment A of formula (1A) or (2A) is arene. In anotherembodiment A of formula (1A) or (2A) is an alkane. In another embodimentA of formula (1A) or (2A) is cycloalkane or saturated heterocycle.

In another embodiment, this invention is directed to aradiation-sensitive composition comprising a carboxylic acid andbromoisocyanurate; wherein said carboxylic acid is represented by thestructure of compound (2B):

wherein Q¹, Q², Q³, Q⁴, and Q⁵, are each independently selected from: H,F, Cl, Br, COOH, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)Cl, C(O)N(R¹)₂, CN,SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹,S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R², N(R¹)SO₂R¹, N(acyl)₂,N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two of Q¹ and Q², Q² and Q³, Q³and Q⁴, or Q⁴ and Q⁵, are joined to form a 5- or 6-membered substitutedor unsubstituted, saturated or unsaturated carbocyclic or heterocyclicring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl orheterocyclyl; wherein R¹ is optionally substituted by R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl,cycloalkyl or heterocyclyl;

wherein if either one of Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (2B) iscarboxylic group COOH, then the respective Q¹, Q², Q³, Q⁴, Q⁵, and/or R²in (1B) is Br.

In one embodiment, this invention is directed to a compositioncomprising an organic bromide of formula (1A):

wherein said organic bromide of formula (1A) is prepared by reacting acarboxylic acid of formula (2A)

and bromoisocyanurate by electromagnetic irradiation;wherein A is arene, alkane, cycloalkane or saturated heterocycle;n is an integer of at least 1;m is an integer of at least 0;each Q is independently F, Cl, Br, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)Cl,C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹,OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R¹, N(R¹)SO₂R¹,N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two vicinal Qsubstituents are joined to form a 5- or 6-membered substituted orunsubstituted, saturated or unsaturated carbocyclic or heterocyclicring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl orheterocyclyl, wherein R¹ is optionally substituted by one or moresubstituents of R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl,cycloalkyl or heterocyclyl;

wherein if either one of R² in (2A) is a carboxylic group COOH, then therespective R² in (1A) is Br;

wherein said position of Br and Q in said structure of formula (1A)correspond to the same position of said COOH and Q, respectively in saidstructure of formula (2A)

In one embodiment, this invention is directed to a compositioncomprising an organic bromide of formula (1B):

wherein said organic bromide of formula (1B) is prepared by reacting acarboxylic acid of formula (2B)

and bromoisocyanurate by electromagnetic irradiation;wherein Q¹, Q², Q³, Q⁴, and Q⁵, are each independently selected from: H,F, Cl, Br, COOH, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)Cl, C(O)N(R¹)₂, CN,SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹,S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R², N(R¹)SO₂R¹, N(acyl)₂,N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two of Q¹ and Q², Q² and Q³, Q³and Q⁴, or Q⁴ and Q⁵, are joined to form a 5- or 6-membered substitutedor unsubstituted, saturated or unsaturated carbocyclic or heterocyclicring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl orheterocyclyl; wherein R¹ is optionally substituted by R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl,cycloalkyl or heterocyclyl;

wherein if either one of Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (2B) iscarboxylic group COOH, then the respective Q¹, Q², Q³, Q⁴, Q⁵, and/or R²in (1B) is Br.

Mechanism of the Bromodecarboxylation Reaction of the Invention

Without bounding to any particular mechanism or theory, it iscontemplated that the process according to this invention is describedas follows:

-   -   i. Bromination of the carboxylic acid R—CO₂H (corresponds to        compounds of formula (2A) and (2B)) with the bromoisocyanurate        to give the corresponding acyl hypobromite, R—CO₂Br, according        to equation (1):

-   -   ii. Homolytic degradation of the acyl hypobromite, R—CO₂Br, to        give carbon-centered free radical R. according to equation (2):

R—CO₂Br→R.+CO₂+Br.  (2)

-   -   iii. R. pulls out a bromine atom from nearest bromine atom donor        to yield bromide R—Br according to equation (3):

R.+bromine atom donor→R—Br  (3)

wherein the bromine atom donor is selected from: bromine radical Br.(equation (2)), additive (e.g. Br₂, bromide, polybromides), or thehalocarbon solvent (e.g., BrCCl₃, CF₃CHBrCl).

It should be noted that the suggested mechanism presented above, is onlya rough scheme of the complex real processes.

One indication for the radical chain mechanism of thebromodecarboxylation reaction is by using a2,2,6,6-tetramethyl-1-piperidinynyloxyl (TEMPO) carbon-centered radicalscavenger as a mechanistic diagnostic tool. Addition of TEMPO as radicalchain inhibitor to the initial reaction mixture of thebromodecarboxylation reaction, inhibits the reaction. Inhibition of thebromodecarboxylation reaction by addition of TEMPO indicates that thereaction has a radical chain mechanism.

According to the present invention, the carbon-centered free radicals R.are obtained by applying photochemical and/or thermal energy to amixture of carboxylic acid R—CO₂H, bromoisocyanurate and, optionally anadditive. The photochemical energy increases the rate of the reaction.

The following examples are presented in order to more fully illustratethe preferred embodiments of the invention. They should in no way,however, be construed as limiting the broad scope of the invention.

EXAMPLES Experimental Details

Reagents: All reagents and solvents were purchased from Sigma-Aldrich,Alfa Aesar, Acros Organics, and TCI unless specified otherwise.3,5,5-Trimethylhydantoin 3,5,5-TMH and 4,4-dimethyl-2-oxazolidinone DMOwere prepared according to published procedure (WO2015068159 A2).

Techniques: All reactions were performed under nitrogen atmosphere innon-flame dried glassware. Mounted nearby the reaction flask 3 W LEDwarm-white lamp was used for irradiation of the reaction mixture.Conversions were determined by ¹H NMR, and yields of isolated productrefer to products with more than 95% purity by ¹H NMR. Flash columnchromatography was performed employing 63-200 μm silica gel 60 accordingto standard techniques (J. Org. Chem. 1978, v. 43, 2923).

Analytical methods: GC analyses were performed on Shimadzu GC-2010 gaschromatograph with flame ionization detector (FID) using a 30 m×0.25 mmQuadrex capillary column with methyl 5% phenyl silicone stationaryphase, 0.25 μm film thickness. For TLC analysis, Merck precoated TLCplates (silica gel 60 F-254 on glass plates, 0.25 mm) were used. NMRspectra were recorded on a Bruker AM-400 (¹H at 400 MHz, ¹³C at 100 MHz)instruments using CDCl₃ (unless otherwise stated) as a solvent. Data arereported as follows: chemical shift in ppm relative to internal TMS,multiplicity, coupling constant in Hz and integration. Compoundsdescribed in the literature were characterized by comparing their ¹Hand/or ¹³C NMR spectra to the previously reported data. New compoundswere further characterized by high-resolution mass spectra.

The following abbreviations are used:

-   1,5,5-TMH=1,5,5-trimethylhydantoin-   1-BTMH=1-bromo-3,5,5-trimethylhydantoin-   3,5,5-TMH=3,5,5-trimethylhydantoin-   3-BTMH=3-bromo-1,5,5-trimethylhydantoin-   ABCN=1,1′-azobis(cyclohexanecarbonitrile)-   AIBN=azobisisobutyronitrile-   Alk=alkyl-   APCI=atmospheric pressure chemical ionization-   Ar=arene-   BDMO=3-bromo-4,4-dimethyl-2-oxazolidinone or    3-bromo-4,4-dimethyloxazolidin-2-one-   BNPT=N-bromo-4-nitrophthalimide-   BPT=N-bromophthalimide-   BNPT=N-bromo-4-nitrophthalimide-   CTAB=cetyltrimethylammonium bromide-   d=doublet-   DBDMH=1,3-dibromo-5,5-dimethylhydantoin-   DBI=dibromoisocyanuric acid-   DCE=1,2-dichloroethane-   DCM=dichloromethane-   DMO=4,4-dimethyl-2-oxazolidinone or 4,4-dimethyloxazolidin-2-one-   FL=fluorescent room lighting-   hv=visible light irradiation-   HRMS=high resolution/accurate mass spectrometer-   LED=light-emitting diode-   LL=LED lamp irradiation-   m=multiplet-   MBCA=monobromoisocyanuric acid-   MCCA=monochloroisocyanuric acid-   N-bromoimide=bromoimide, wherein bromine atom is attached directly    to nitrogen atom-   NBS=N-bromosuccinimide-   NBSac=N-bromosaccharine-   NL=dark-   NMR=nuclear magnetic resonance-   ppm=part per million-   rt=room temperature-   s=singlet-   SDS=sodium dodecyl sulfate-   t=triplet-   TL=tungsten lamp irradiation-   TBCA=tribromoisocyanuric acid-   TEMPO=2,2,6,6-tetramethyl-1-piperidinyloxy, free radical-   Δ=heating

Example 1 Preparation of N-bromoamides

General Method A:

A mixture of amide (1.0 mmol), PhI(OAc)₂ (0.6 mmol), Br₂ (0.8 mmol), andMeCN (5-10 mL) was stirred at rt for 3-40 h and then concentrated invacuo. CCl₄, cyclohexane, or benzene (5-10 mL) was added to the residueand the obtained mixture was stirred for 15 min at rt and 1 h at 0 to 5°C. The precipitated solid was filtered, washed on the filter with coldCCl₄, cyclohexane, or benzene and dried in vacuo to give the desiredN-bromoimide as an off-white powder.

General Method B:

A mixture of amide (1.0 mmol), PhI(OAc)₂ (0.6 mmol), Br₂ (0.8 mmol), andCCl₄, benzene, or cyclohexane (5-10 mL) was stirred for 4-40 h at rt andfor 1 h at 0 to 5° C. The precipitated solid was filtered, washed on thefilter with cold CCl₄, benzene, or cyclohexane and dried in vacuo togive N-bromoimide as an off-white powder. The results are listed inTable 1.

Note: In cases where more than one N—H group exists in the amidestarting material, the amounts of PhI(OAc)₂ and Br₂ is multiplied by thenumber of N—H groups.

TABLE 1 Preparation of N-bromoamides N-Bromo- Yield, entry amide Methodamide % 1 succinimide A NBS 92 2 succinimide B NBS up to 94 3 saccharinA NBSac 86 4 saccharin B NBSac 50 5 pthalimide A BPT 90 6 pthalimide BBPT 70 7 4-nitrophthalimide A BNPT 88 8 4-nitrophthalimide B BNPT 90 9DMH B DBDMH 97 10 DPH A DBDPH 80 11 3,5,5-TMH A 1-BTMH 86 12 DMO A BDMO84 13 DMO B BDMO up to 76

Entries 1-2: N-Bromosuccinimide, NBS ¹H NMR: δ 2.96 (s, 4H) ppm; ¹³CNMR: δ 173.2, 28.8 ppm.

Entries 3-4: N-Bromosaccharin, NBSac ¹H NMR (CD₃CN): δ 8.10-8.00 (m,2H), 7.99-7.87 (m, 2H) ppm; ¹³C NMR (CD₃CN): δ 159.6, 139.3, 136.5,135.9, 128.2, 126.4, 122.5 ppm.

Entries 5-6: N-Bromophthalimide, BPT ¹H NMR (CD₃CN): δ 7.84-7.76 (m, 4H)ppm; ¹³C NMR (CD₃CN): δ 166.7, 135.3, 133.4, 124.2 ppm.

Entries 7-8: N-Bromo-4-nitrophthalimide, BNPT ¹H NMR (CD₃CN): δ 8.58 (d,J=8.5 Hz, 1H), 8.55 (s, 1H) 8.04 (d, J=8.5 Hz, 1H) ppm; ¹³C NMR (CD₃CN):δ 165.2, 164.9, 152.6, 137.6, 134.3, 130.5, 125.6, 119.3 ppm.

Entry 9: 1,3-Dibromo-5,5-dimethylhydantoin in benzene, DBDMH ¹H NMR: δ1.46 (s, 6H) ppm; ¹³C NMR: δ 172.2, 151.5, 68.9, 23.9 ppm.

Entry 10: 1,3-Dibromo-5,5-diphenylhydantoin, DBDPH ¹H NMR (CD₃CN): δ7.51-7.43 (m, 6H), 7.32-7.28 (m, 4H) ppm; ¹³C NMR (CD₃CN): δ 171.4,153.3, 137.0, 130.5, 129.7, 129.6, 129.3, 129.2, 80.1 ppm.

Entry 11: 1-Bromo-3,5,5-trimethylhydantoin, 1-BTMH ¹H NMR: δ 3.06 (s,3H), 1.38 (s, 6H) ppm; ¹³C NMR: δ 174.7, 155.1, 66.1, 26.0, 23.3 ppm.

Entries 12-13: 3-Bromo-4,4-dimethyl-2-oxazolidinone, BDMO ¹H NMR: δ 4.19(s, 2H), 1.29 (s, 6H) ppm; ¹³C NMR: δ 157.3, 74.8, 62.9, 24.1 ppm

Example 2 Comparative Examples

A. Attempts to Bromodecarboxylate Arenecarboxylic Acids withN-Bromosuccinimide (NBS) Under Heterolytic Reaction Conditions Disclosedin IN803DEL1999

The reactions were conducted under fluorescent room lighting (FL).

Example 2A-1

An attempt to bromodecarboxylate benzoic acid using tetrabutylammoniumtrifluororacetate as catalyst

A mixture of benzoic acid (0.44 g, 3.60 mmol), N-bromosuccinimide NBS(0.60 g, 3.37 mmol), tetrabutylammonium trifluororacetate [NBu₄]OAc_(F)(0.24 g, 0.67 mmol) and 1,2-dichloroethane DCE (6 mL) was stirred at rtfor 24 h. The reaction mixture was washed with 1 M aq Na₂SO₃, dried overNa₂SO₄, and filtered through short neutral alumina pad.

The obtained filtrate did not contain bromobenzene (GC data,1-chlro-2-fluorobenzene was used as internal standard).

Example 2A-2

An attempt to bromodecarboxylate p-toluic acid using tetrabutylammoniumtrifluororacetate as catalyst

A mixture of p-toluic acid (0.48 g, 3.52 mmol), N-bromosuccinimide NBS(0.60 g, 3.37 mmol), tetrabutylammonium trifluororacetate [NBu₄]OAc_(F)(0.24 g, 0.67 mmol) and 1,2-dichloroethane DCE (6 mL) was stirred at rtfor 20 h. The reaction mixture was washed with 1 M aq Na₂SO₃, dried overNa₂SO₄, and filtered through short neutral alumina pad.

The obtained filtrate did not contain p-bromotoluene (GC data,o-dichlorobenzene was used as internal standard).

Example 2A-3

An attempt to bromodecarboxylate p-anisic acid using tetrabutylammoniumtrifluororacetate as catalyst

A mixture of p-anisic acid (0.52 g, 3.42 mmol), N-bromosuccinimide NBS(0.60 g, 3.37 mmol), tetrabutylammonium trifluororacetate [NBu₄]OAc_(F)(0.24 g, 0.67 mmol) and 1,2-dichloroethane DCE (6 mL) was stirred at rtfor 18 h. The reaction mixture was washed with 1 M aq Na₂SO₃, dried overNa₂SO₄, and filtered through short neutral alumina pad.

The obtained filtrate did not contain p-bromoanisol (GC data,1,2,4-trichlorobenzene was used as internal standard).

B. Attempts to Bromodecarboxylate Arenecarboxylic Acids withN-Bromosuccinimide (NBS) Under Heterolytic Reaction Conditions Disclosedin J. Dispersion Sci. Technol. 2007, v. 28, 613

Example 2B-1

An attempt to bromodecarboxylate 2-bromobenzoic acid usingcetyltrimethylammonium bromide as catalyst

A mixture of 2-bromobenzoic acid (0.20 g, 1.0 mmol), N-bromosuccinimideNBS (0.27 g, 1.5 mmol), cetyltrimethylammonium bromide CTAB (1.82 g, 5.0mmol) and 1,2-dichloroethane DCE (10 mL) was stirred under refluxconditions in dark for 3 h. After it was cooled, the reaction mixturewas washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, filtered through shortneutral alumina pad and concentrated in vacuo to give 0.21 g (79%) of2-chloroethyl 2-bromobenzoate 2-BrC₆H₄CO₂(CH₂)₂Cl.

¹H NMR: δ 7.85 (d, J=7 Hz, 1H), 7.64 (d, J=7 Hz, 1H), 7.38-7.28 (m, 2H)4.56 (t, J=6 Hz, 2H), 3.80 (t, J=6 Hz, 2H) ppm.

Example 2B-2

An attempt to bromodecarboxylate 2-bromobenzoic acid using sodiumdodecyl sulfate as catalyst

A mixture of 2-bromobenzoic acid (0.20 g, 1.0 mmol), N-bromosuccinimideNBS (0.27 g, 1.5 mmol), sodium dodecyl sulfate SDS (1.44 g, 5.0 mmol)and 1,2-dichloroethane DCE (10 mL) was stirred in dark for 3 h underreflux conditions. After it was cooled, the reaction mixture was washedwith 1 M aq Na₂SO₃, dried over Na₂SO₄, filtered through short neutralalumina pad and concentrated in vacuo.

The residue (15 mg) did not contain 1,2-dibromobenzene by ¹H NMR.

Example 3 N-Bromoamides as Reagents for Radical BromodecarboxylationN-Bromoamides Induced Bromodecarboxylation of 2-Bromobenzoic Acid

A mixture of 2-bromobenzoic acid (1 mmol), N-bromoamide, additive(optionally) and solvent (10 mL) was stirred under fluorescent roomlight illumination (FL). The reaction mixture was concentrated in vacuo.A solution of the residue in CDCl₃ was filtered directly to NMR tube.Conversion of the reaction was determined by ¹H NMR. The results arepresented in Table 2.

TABLE 2 N-Bromoamides as reagents for radical bromodecarboxylation ^(a)entry Reaction conditions conversion, % 1 DBI 1 mol/DCM, rt FL 24 h 1002 DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 100 3 NBS 1 mol/DCM, rt FL 24 h 04 NBS 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 0 5 DBDMH 1 mol/DCM, rt FL 24 h 06 DBDMH 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 6 7 BTMH 1 mol/DCM, rt FL 24 h 08 BTMH 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 0 9 BDMO 1 mol/DCM, rt FL 24 h 010 BDMO 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 1 11 BPT 1 mol/DCM, rt FL 24 h 012 BPT 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 7 13 BNPT 1 mol/DCM, rt FL 24 h 014 BNPT 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 0 15 NBSac 1 mol/DCM, rt FL 24 h4 16 NBSac 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 17 ^(a) All quantities inmole/mole of 2-bromobenzoic acid.

Bromodecarboxylation of 2-bromobenzoic acid with1,3-dibromo-5,5-dimethylhydantoin

A mixture of 2-bromobenzoic acid (0.20 g, 1 mmol),1,3-dibromo-5,5-dimethylhydantoin DBDMH (0.29 g, 1 mmol) and1,2-dichloroethane DCE (5 mL) was irradiated with 250 W tungsten lampunder reflux conditions for 15 h. The cooled reaction mixture was washedwith 1 M aq Na₂SO₃, dried over Na₂SO₄, filtered through short neutralalumina pad and concentrated in vacuo. The residue was purified bychromatography on silica gel (eluent: hexane) to give 50 mg (20%) of1,2-dibromobenzene.

¹H NMR: δ 7.65-7.59 (m, 2H), 7.19-7.14 (m, 2H) ppm.

Bromodecarboxylation of 2-bromobenzoic acid with N-bromosuccinimide

A mixture of 2-bromobenzoic acid (0.20 g, 1 mmol), N-bromosuccinimideNBS (0.36 g, 2 mmol) and 1,2-dichloroethane DCE (5 mL) was irradiatedwith 250 W tungsten lamp under reflux conditions for 15 h. The cooledreaction mixture was washed with 1 M aq Na₂SO₃, dried over Na₂SO₄,filtered through short neutral alumina pad and concentrated in vacuo.The residue was purified by chromatography on silica gel (eluent:hexane) to give 10 mg (4%) of 1,2-dibromobenzene.

Example 4 Bromodecarboxylation of 2-Bromobenzoic Acid Induced byBromoisocyanurate Optimization of the Reaction Conditions

A round bottom flask equipped with Dimroth condenser (chilled to 10° C.)was charged with 2-bromobenzoic acid (1 mmol), bromoisocyanurate,additive (optionally) and solvent (10 mL). The mixture was stirred at rtor heated in an oil bath. The reaction was provided in the dark (NL) orunder florescent room light irradiation (FL). The cold reaction mixturewas concentrated in vacuo. The residue was dissolved in CDCl₃ andfiltered directly to NMR tube. Conversion was determined by ¹H NMR. Theresults are presented in Table 3.

TABLE 3 Bromodecarboxylation of 2-bromobenzoic acid ^(a) entry Reactionconditions conversion, % 1 Br₂ 2 mol/DCM, rt FL 24 h 0 2 DBI 0.5mol/DCM, 60° FL 24 h 30 3 DBI 0.75 mol/DCM, 60° FL 24 h 56 4 DBI 1mol/DCM, rt FL 24 h 100 5 DBI 1 mol/Br₂ 0.5 mol/DCM, rt FL 24 h 100 6DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 100 7 DBI 1 mol/Br₂ 2 mol/DCM, rt FL24 h 100 8 DBI 1 mol/Br₂ 4 mol/DCM, rt FL 24 h 100 9 DBI 1 mol/BrCCl₃,rt FL 24 h 0 10 DBI 1 mol/BrCCl₃, 120° FL 1 h 11 11 DBI 1 mol/Br₂ 2mol/BrCCl₃, rt FL 24 h 0 12 DBI 1 mol/Br₂ 2 mol/BrCCl₃, 120° FL 1 h 10013 DBI 1 mol/Br₂ 2 mol/BrCCl₃, 120° NL, 1 h 39 14 DBI 1 mol/Br₂ 2mol/BrCCl₃, 120° NL 3 h 100 15 DBI 1 mol/CCl₄, 100° FL 1 h 0 16 DBI 1mol/Br₂ 2 mol/CCl₄, 100° FL 6 h 100 17 DBI 1 mol/CHCl₃, rt FL 24 h 0 18DBI 1 mol/DCE, rt FL 24 h 6 19 DBI 1 mol/PhH, rt FL 24 h 0 20 DBI 1mol/PhCl, rt FL 24 h 0 21 DBI 1 mol/PhCF₃, rt F, 24 h 0 22 DBI 1mol/C₆H₁₂, rt FL 24 h 0 23 DBI 1 mol/EtOAc, rt FL 24 h 0 24 DBI 1mol/MeCN, rt FL 24 h 33 25 DBI 1 mol/MeNO₂, rt FL 24 h 0 ^(a) Allquantities in mole/mole of 2-bromobenzoic acid. Oil bath temperatures indegrees Celsius.

Example 5 Bromodecarboxylation of Arenecarboxylic Acids Optimizing ofthe Reactions

Mixture of arenecarboxylic acid (1 mmol), bromoisocyanurate, additive(optionally) and solvent (10 mL) was stirred under fluorescent roomlight irradiation (FL). An aliquot of the reaction mixture wasconcentrated in vacuo. The residue was dissolved in CDCl₃ and filtereddirectly to NMR tube. Conversion was determined by ¹H NMR. The resultsare presented in Table 4.

TABLE 4 Bromodecarboxylation of arenecarboxylic acids ArCO₂H ^(a) entryArCO₂H Reaction conditions ^(a) conversion, % 1 2-NO₂C₆H₄CO₂H DBI 1mol/DCM, rt FL 24 h 65 2 2-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, 100 rtFL 24 h 3 2-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 2 mol/DCM, 100 rt FL 24 h 42-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 3 mol/DCM, 100 rt FL 24 h 5 2-NO₂C₆H₄CO₂HDBI 1 mol/Br₂ 4 mol/DCM, 100 rt FL 24 h 6 3-NO₂C₆H₄CO₂H DBI 1 mol/DCM,rt FL 24 h 18 7 3-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, 100 rt FL 24 h 83-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 2 mol/DCM, 100 rt FL 24 h 9 3-NO₂C₆H₄CO₂HDBI 1 mol/Br₂ 3 mol/DCM, 100 rt FL 24 h 10 3-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 4mol/DCM, 100 rt FL 24 h 11 4-NO₂C₆H₄CO₂H DBI 1 mol/DCM, rt FL 24 h 50 124-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 4 mol/DCM, 70 rt FL 24 h 13 4-NCC₆H₄CO₂H DBI1 mol/DCM, rt FL 24 h 55 14 4-NCC₆H₄CO₂H DBI 1 mol/Br₂ 4 mol/DCM, 85 rtFL 24 h ^(a) All quantities in mole/mole of arenecarboxylic acid.

Example 6 Bromoisocyanurate Induced Radical Bromodecarboxylation ofArenecarboxylic Acids

A mixture of arenecarboxylic acid ArCO₂H (1 mmol), bromoisocyanurate,additive and solvent (10 mL) was stirred under fluorescent room light(FL) or warm-white 3 W LED (LL) irradiation (hv). The reaction mixturewashed with 1 M aq Na₂SO₃, dried over Na₂SO₄, filtered through shortneutral alumina pad and concentrated in vacuo to yield crude bromoareneArBr. Optionally, the crude bromide was purified by chromatography onsilica gel. The results are presented in Table 5.

TABLE 5 Bromodecarboxylation of arenecarboxylic acids ArCO₂H ^(a) yield,% entry ArCO₂H Reaction conditions ArBr  1 2-BrC₆H₄CO₂H DBI 1 mol/Br₂ 1mol/DCM, rt FL 24 h 97  2 3-BrC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24h 92  3 4-BrC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 82  42-ClC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 98  5 3-ClC₆H₄CO₂H DBI1 mol/Br₂ 1 mol/DCM, rt FL 24 h 89  6 4-ClC₆H₄CO₂H DBI 1 mol/Br₂ 1mol/DCM, rt FL 24 h 88  7 2,4-Cl₂C₆H₃CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL24 h 97  8 2-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 99  93-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 99 10 4-NO₂C₆H₄CO₂HDBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 60 11 3-CNC₆H₄CO₂H DBI 1 mol/Br₂ 1mol/DCM, rt FL 24 h 66 12 4-CNC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24h 95 13 2-Br-5-FC₆H₃CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 96 145-Br-2-FC₆H₃CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 36 155-Br-2-FC₆H₃CO₂H DBI 1 mol/Br₂ 2 mol/DCM, 60° FL 24 h 89 164-Cl-2-FC₆H₃CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 60 174-NO₂-2-CF₃C₆H₃CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 20 184-NO₂-2-CF₃C₆H₃CO₂H DBI 1 mol/Br₂ 2 mol/DCM, 60° FL 24 h 92 194-NO₂-3-CF₃C₆H₃CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 45 202-MeO₂CC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 98 213-MeO₂CC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 98 224-MeO₂CC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 97 233-NO₂-4-MeO₂CC₆H₃CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 75 242-PhtNC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 99 25 trimelliticanhydride DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 70 26

DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 71 27 3,5-Br₂C₆H₃CO₂H DBI 1 mol/Br₂1 mol/DCM, rt FL 24 h 51 (GC) 28 3,4-F₂C₆H₃CO₂H DBI 1 mol/Br₂ 2mol/CBrCl₃, 120° LL 24 h 77 (GC) 29 2,4,5-F₃C₆H₂CO₂H DBI 1 mol/Br₂ 2mol/CBrCl₃, 120° LL 24 h 95 (GC) 30 3,4,5-F₃C₆H₂CO₂H DBI 1 mol/Br₂ 2mol/CBrCl₃, 120° LL 24 h 86 (GC) 31 C₆F₅CO₂H DBI 1 mol/Br₂ 1 mol/CBrCl₃,120° LL 24 h 70 (GC) ^(a) All quantities in mole/mole of arenecarboxylicacid. Oil bath temperatures in degrees Celsius.

Entry 1: 1,2-Dibromobenzene ¹H NMR: δ 7.62 (dd, J=6, 4 Hz, 2H), 7.16(dd, J=6, 4 Hz, 2H) ppm; ¹³C NMR: δ 133.9, 128.6, 124.9 ppm.

Entry 2: 1,3-Dibromobenzene ¹H NMR: δ 7.67 (t, J=2 Hz, 1H), 7.43 (dd,J=8, 2 Hz, 2H), 7.1 (t, J=8 Hz, 1H) ppm; ¹³C NMR: δ 134.3, 131.2, 130.3,123.1 ppm.

Entry 3: 1,4-Dibromobenzene ¹H NMR: δ 7.35 (s, 4H) ppm; ¹³C NMR: δ133.2, 121.1 ppm.

Entry 4: 1-Bromo-2-chlorobenzene ¹H NMR: δ 7.61 (dd, J=8, 1.4 Hz, 1H),7.45 (dd, J=8, 1.4 Hz, 1H), 7.24 (td, J=8, 1.4 Hz, 1H), 7.11 (td, J=8,1.4 Hz, 1H) ppm; ¹³C NMR: δ 134.6, 133.9, 130.5, 128.5, 127.9, 122.6ppm.

Entry 5: 1-Bromo-3-chlorobenzene ¹H NMR: δ 7.52 (t, J=2 Hz, 1H), 7.39(d, J=8 Hz, 1H), 7.28 (d, J=8 Hz, 1H), 7.16 (t, J=8 Hz, 1H) ppm; ¹³CNMR: δ 135.3, 131.6, 130.9, 129.9, 127.4, 122.9 ppm.

Entry 6: 1-Bromo-4-chlorobenzene ¹H NMR: δ 7.42 (dt, J=9, 3 Hz, 2H),7.10-7.22 (m, 2H) ppm; ¹³C NMR: δ 133.3, 132.9, 130.3, 120.4 ppm.

Entry 7: 1-Bromo-2,4-dichlorobenzene ¹H NMR: δ 7.52 (d, J=9 Hz, 1H),7.45 (d, J=2 Hz, 1H), 7.10 (dd, J=9, 2 Hz, 1H) ppm; ¹³C NMR: δ 135.5,134.4, 133.9, 130.3, 128.3, 120.8 ppm.

Entry 8: 1-Bromo-2-nitrobenzene ¹H NMR: δ 7.84 (dd, J=8, 2 Hz, 1H), 7.74(dd, J=8, 2 Hz, 1H), 7.49-7.40 (m, 2H) ppm; ¹³C NMR: δ 150.1, 135.2,133.3, 128.3, 125.7, 114.6 ppm.

Entry 9: 1-Bromo-3-nitrobenzene ¹H NMR: δ 8.38 (t, J=1 Hz, 1H), 8.17(dd, J=8, 1 Hz, 1H), 7.83 (dd, J=8, 1 Hz, 1H), 7.44 (t, J=8 Hz, 1H) ppm;¹³C NMR: δ 148.9, 137.7, 130.7, 126.9, 123.0, 122.2 ppm.

Entry 10: 1-Bromo-4-nitrobenzene ¹H NMR: δ 8.08 (d, J=9 Hz, 2H), 7.67(d, J=9 Hz, 2H) ppm; ¹³C NMR: δ 147.1, 132.7, 130.1, 125.1 ppm.

Entry 11: 3-Bromobenzonitrile ¹H NMR: δ 7.79 (s, 1H), 7.74 (d, J=8 Hz,1H), 7.60 (d, J=8 Hz, 1H), 7.36 (t, J=8 Hz, 1H) ppm; ¹³C NMR: δ 136.2,134.9, 130.8, 130.7, 123.0, 117.4, 114.3 ppm.

Entry 12: 4-Bromobenzonitrile ¹H NMR: δ 7.63 (d, J=9 Hz, 2H), 7.52 (d,J=9 Hz, 2H) ppm; ¹³C NMR: δ 133.5, 132.7, 128.1, 118.1, 111.4 ppm.

Entry 13: 1,2-Dibromo-4-fluorobenzene ¹H NMR: δ 7.57 (dd, J=9, 6 Hz,1H), 7.37 (dd, J=8, 3 Hz, 1H), 6.29 (td, J=6, 39 Hz, 1H) ppm; ¹³C NMR: δ161.5 (d, J_(CF)=251 Hz), 134.4 (d, J_(CF)=9 Hz), 125.3 (d, J_(CF)=10Hz), 121.3, 121.1, 119.7 (d, J_(CF)=4 Hz) ppm.

Entries 14-15: 2,4-Dibromo-1-fluorobenzene ¹H NMR: δ 7.69 (dd, J=6, 2Hz, 1H), 7.39 (ddd, J=9, 4, 2 Hz, 1H), 7.01 (t, J=9 Hz, 1H) ppm; ¹³CNMR: δ 158.5 (d, J_(CF)=248 Hz), 136.0, 132.1 (d, J_(CF)=7 Hz), 117.9(d, J_(CF)=24 Hz), 117.1 (d, J_(CF)=4 Hz), 110.3 (d, J_(CF)=22 Hz), ppm.

Entry 16: 1-Bromo-4-chloro-2-fluorobenzene ¹H NMR: δ 7.47 (t, J=8 Hz,1H), 7.15 (dd, J=8, 2 Hz, 1H), 7.04 (d, J=8 Hz, 1H) ppm; ¹³C NMR: δ159.1 (d, J_(CF)=250 Hz), 134.1, 125.8 (d, J_(CF)=4 Hz), 117.5 (d,J_(CF)=25 Hz), 107.4 (d, J_(CF)=21 Hz) ppm.

Entry 17-18: 1-Bromo-4-nitro-2-(trifluoromethyl)benzene ¹H NMR: δ 8.50(d, J=2 Hz, 1H), 8.26 (dd, J=9, 2 Hz, 1H), 7.96 (d, J=9 Hz, 1H) ppm; ¹³CNMR: δ 146.9, 136.5, 131.8 (d, J_(CF)=33 Hz), 127.7, 127.5, 123.2 (q,J_(CF)=6 Hz), 122.0 (q, J_(CF)=274 Hz) ppm; ¹⁹F NMR: δ −66.4 ppm.

Entry 19: 4-Bromo-1-nitro-2-(trifluoromethyl)benzene ¹H NMR: δ 7.97 (d,J=2 Hz, 1H), 7.87 (dd, J=9, 2 Hz, 1H), 7.80 (d, J=9 Hz, 1H) ppm; ¹³CNMR: δ 147.0, 136.3, 131.4 (q, J_(CF)=11, 5 Hz), 127.4, 126.7, 125.5 (d,J_(CF)=35 Hz), 121.2 (q, J_(CF)=274 Hz) ppm; ¹⁹F NMR: δ −63.3 ppm.

Entry 20: Methyl 2-bromobenzoate ¹H NMR: δ 7.74 (d, J=8 Hz, 1H), 7.60(d, J=8 Hz, 1H), 7.34-7.24 (m, 2H), 3.88 (s, 3H) ppm; ¹³C NMR: δ 166.5,134.3, 132.5, 132.1, 131.2, 127.1, 121.6, 52.4 ppm.

Entry 21: Methyl 3-bromobenzoate ¹H NMR: δ 8.16 (s, 1H), 7.95 (d, J=8Hz, 1H), 7.66 (d, J=8 Hz, 1H), 7.30 (t, J=8 Hz, 3H), 3.91 (s, 3H) ppm;¹³C NMR: δ 165.8, 135.9, 132.7, 132.1, 130.0, 128.2, 122.5, 55.5 ppm

Entry 22: Methyl 4-bromobenzoate ¹H NMR: δ 7.89 (d, J=8 Hz, 2H), 7.57(d, J=8 Hz, 2H), 3.91 (s, 3H) ppm; ¹³C NMR: δ 166.5, 131.8, 131.2,129.1, 128.1, 52.4 ppm.

Entry 23: Methyl 4-bromo-2-nitrobenzoate ¹H NMR: δ 8.00 (d, J=2 Hz, 1H),7.79 (dd, J=8, 2 Hz, 1H), 7.64 (d, J=2 Hz, 1H), 3.90 (s, 3H) ppm; ¹³CNMR: δ 164.9, 149.0, 135.9, 131.4, 127.1, 125.9, 125.8, 53.5 ppm.

Entry 24: 1-Bromo-2-phthalimidobenzene ¹H NMR: δ 8.00-7.95 (m, 2H),7.84-7.78 (m, 2H), 7.74 (dd, J=8, 1 Hz, 1H), 7.47 (dt, J=8, 1 Hz, 1H),7.40-7.32 (m, 2H) ppm; ¹³C NMR: δ 166.7, 134.6, 133.7, 132.0, 131.5,131.0, 130.9, 128.5, 124.1, 123.4 ppm;

Entry 25: 4-Bromophthalic anhydride ¹H NMR: δ 8.16 (d, J=1 Hz, 1H), 8.04(dd, J=8, 1 Hz, 1H), 7.88 (d, J=8 Hz, 1H) ppm; ¹³C NMR: δ 161.9, 161.5,139.4, 133.0, 131.6, 129.9, 129.0, 127.0 ppm.

Entry 26: N-(tert-Butyl)-4-bromophthalimide ¹H NMR: δ 7.88 (d, J=1 Hz,1H), 7.80 (dd, J=8, 1 Hz, 1H), 7.62 (d, J=8 Hz, 1H), 1.68 (s, 3H) ppm;¹³C NMR: δ 168.9, 168.3, 136.8, 133.9, 130.8, 128.6, 126.1, 124.2, 58.3,29.1 ppm.

Example 7 Bromodecarboxylation of Arenedicarboxylic Acids Induced byBromoisocyanurate

Round bottom flask equipped with Dimroth condenser (chilled to 10° C.)was charged with arenedicarboxylic acid RC₆H₃(CO₂H)₂ (1 mmol),bromoisocyanurate, additive and solvent (10 mL). The mixture wasmagnetically stirred and heated in an oil bath at 120° C. underflorescent room light irradiation (FL) for 60 h. The cooled reactionmixture was filtered through short silica gel pad, washed with 1 M aqNa₂SO₃, dried over Na₂SO₄, filtered and concentrated in vacuo to givecrude dibromoarene RC₆H₃Br₂. Optionally, the crude dibromide waspurified by chromatography on silica gel. The results are presented inTable 6.

TABLE 6 Bromodecarboxylation of arenedicarboxylic acids RC₆H₃(CO₂H)₂^(a) Yield, % entry RC₆H₃(CO₂H)₂ Reaction conditions RC₆H₃Br₂ 14-NO₂-1,2-C₆H₃(CO₂H)₂ DBI 2 mol/Br₂ 2 mol/ 32 BrCCl₃, 120° FL 2 h 21,3-C₆H₄(CO₂H)₂ DBI 2 mol/Br₂ 2 mol/ 6 BrCCl₃, 120° FL 2 h 31,3-C₆H₄(CO₂H)₂ DBI 2 mol/Br₂ 2 mol/ 12 BrCCl₃, 120° FL 24 h 41,3-C₆H₄(CO₂H)₂ DBI 2 mol/Br₂ 2 mol/ 17 BrCCl₃, 120° FL 60 h 55-NO₂-1,3-C₆H₃(CO₂H)₂ DBI 2 mol/Br₂ 2 mol/ 17 BrCCl₃, 120° FL 2 h 65-NO₂-1,3-C₆H₃(CO₂H)₂ DBI 2 mol/Br₂ 2 mol/ 20 BrCCl₃, 120° FL 24 h 75-NO₂-1,3-C₆H₃(CO₂H)₂ DBI 2 mol/Br₂ 2 mol/ 25 BrCCl₃, 120° FL 60 h 81,4-C₆H₄(CO₂H)₂ DBI 2 mol/Br₂ 2 mol/ 12 BrCCl₃, 120° FL 2 h ^(a) Allquantities in mole/mole of arenedicarboxylic acid. Oil bath temperaturesin degrees Celsius.

Example 8 Bromoisocyanurate Induced Radical Bromodecarboxylation ofAlkanoic Acids

Bromodecarboxylation of Lauric Acid: Optimization of the ReactionConditions

A mixture of lauric acid (0.5 mmol), bromoisocyanurate, additive(optionally), and DCM (4 mL) was stirred under fluorescent room light(FL) or warm-white 3 W LED lamp irradiation (LL), or in the dark (NL).An aliquot of the reaction mixture washed with 1 M aq Na₂SO₃, dried overNa₂SO₄, and filtered through short neutral silica gel pad. The yield of1-bromoundecane was determined by gas chromatography (GC) using1,2,4,5-tetrachlorobenzene as internal standard. The results arepresented in Table 7.

TABLE 7 Bromodecarboxylation of lauric acid ^(a) yield, entry Reactionconditions % ^(b)  1 DBI 1 mol/DCM, rt FL 1 h  0  2 DBI 1 mol/DCM, rt FL4 h  0  3 DBI 1 mol/DCM, rt FL 21 h  58  4 DBI 1 mol/Br₂ 0.1 mol/DCM, rtFL 1 h  8  5 DBI 1 mol/Br₂ 0.1 mol/DCM, rt FL 2 h  17  6 DBI 1 mol/Br₂0.1 mol/DCM, rt FL 3 h  24  7 DBI 1 mol/Br₂ 0.1 mol/DCM, rt FL 4 h  31 8 DBI 1 mol/Br₂ 0.2 mol/DCM, rt FL 1 h  20  9 DBI 1 mol/Br₂ 0.2mol/DCM, rt FL 2 h  39  10 DBI 1 mol/Br₂ 0.2 mol/DCM, rt FL 3 h  62  11DBI 1 mol/Br₂ 0.2 mol/DCM, rt FL 4 h  79  12 DBI 1 mol/Br₂ 0.2 mol/DCM,rt FL 5 h  79  13 DBI 1 mol/Br₂ 0.3 mol/DCM, rt FL 1 h  25  14 DBI 1mol/Br₂ 0.3 mol/DCM, rt FL 2 h  51  15 DBI 1 mol/Br₂ 0.3 mol/DCM, rt FL3 h  72  16 DBI 1 mol/Br₂ 0.3 mol/DCM, rt FL 4 h  83  17 DBI 1 mol/Br₂0.3 mol/DCM, rt FL 5 h  80  18 DBI 1 mol/Br₂ 0.4 mol/DCM, rt FL 1 h  23 19 DBI 1 mol/Br₂ 0.4 mol/DCM, rt FL 2 h  50  20 DBI 1 mol/Br₂ 04mol/DCM, rt FL 3 h  70  21 DBI 1 mol/Br₂ 0.4 mol/DCM, rt FL 4 h  80  22DBI 1 mol/Br₂ 0.5 mol/DCM, rt FL 1 h  36  23 DBI 1 mol/Br₂ 0.5 mol/DCM,rt FL 2 h  70  24 DBI 1 mol/Br₂ 0.5 mol/DCM, rt FL 3 h  82  25 DBI 1mol/Br₂ 0.5 mol/DCM, rt FL 4 h  71  26 DBI 1 mol/Br₂ 1 mol/DCM, rt FL 1h  43  27 DBI 1 mol/Br₂ 1 mol/DCM, rt FL 2 h  73  28 DBI 1 mol/Br₂ 1mol/DCM, rt FL 3 h  70  29 DBI 1 mol/Br₂ 1 mol/DCM, rt FL 4 h  60  30DBI 1 mol/Br₂ 2 mol/DCM, rt FL 1 h  55  31 DBI 1 mol/Br₂ 2 mol/DCM, rtFL 2 h  78  32 DBI 1 mol/Br₂ 2 mol/DCM, rt FL 3 h  70  33 DBI 1 mol/Br₂0.3 mol/DCM, rt NL 2 h  1  34 DBI 1 mol/Br₂ 0.3 mol/DCM, rt NL 4 h  2 35 DBI 1 mol/Br₂ 0.3 mol/DCM, rt NL 8 h  3  36 DBI 1 mol/Br₂ 0.3mol/DCM, rt NL 24 h  4  37 DBI 1 mol/Br₂ 0.3 mol/DCM, 3° FL 2 h  8  38DBI 1 mol/Br₂ 0.3 mol/DCM, 3° FL 4 h  19  39 DBI 1 mol/Br₂ 0.3 mol/DCM,3° FL 8 h  41  40 DBI 1 mol/Br₂ 0.3 mol/DCM, 3° FL 24 h  79  41 DBI 1mol/I₂ 0.3 mol/DCM, rt FL 1 h  0  42 DBI 1 mol/I₂ 0.3 mol/DCM, rt FL 2 h 9  43 DBI 1 mol/I₂ 0.3 mol/DCM, rt FL 5.5 h  31  44 DBI 1 mol/I₂ 0.3mol/DCM, rt FL 19 h  35  45 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 1 h 25  46 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 2 h  62  47 DBI 1mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 3 h  84  48 DBI 1 mol/[NBu₄]Br₃ 0.3mol/DCM, rt FL 4 h  98  49 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 5 h 96  50 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 20 h  71  51 DBI 1mol/[NBu₄]Br₃ 0.1 mol/DCM, rt FL 4 h  78  52 DBI 1 mol/[NBu₄]Br₃ 0.1mol/DCM, rt FL 5 h  92  53 DBI 1 mol/[NBu₄]Br₃ 0.1 mol/DCM, rt FL 6 h 95  54 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/TEMPO 0.1 mol/DCM, rt FL 1 h  0  55DBI 1 mol/[NBu₄]Br₃ 0.3 mol/TEMPO 0.1 mol/DCM, rt FL 2 h  0  56 DBI 1mol/[NBu₄]Br₃ 0.3 mol/TEMPO 0.1 mol/DCM, rt FL 4 h  1  57 DBI 1mol/[NBu₄]Br₃ 0.3 mol/DCM, rt LL 1 h  82  58 DBI 1 mol/[NBu₄]Br₃ 0.3mol/DCM, rt LL 2 h  66  59 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, 0° LL 1 h 67  60 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, 0° LL 2 h  93  61 DBI 1mol/[NBu₄]Br₃ 0.3 mol/DCM, 0° LL 3 h 100  62 DBI 1 mol/[NBu₄]Br₃ 0.3mol/DCM, 0° LL 4 h  95  63 DBI 0.5 mol/[NBu₄]Br₃ 0.3 mol/DCM, 0° LL 1 h 40  64 DBI 0.5 mol/[NBu₄]Br₃ 0.3 mol/DCM, 0° LL 2 h  70  65 DBI 0.5mol/[NBu₄]Br₃ 0.3 mol/DCM, 0° LL 3 h  78  66 DBI 0.5 mol/[NBu₄]Br₃ 0.3mol/DCM, 0° LL 4 h  79  67 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, −20° LL 1 h 5  68 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, −20° LL 2 h  11  69 DBI 1mol/[NBu₄]Br₃ 0.3 mol/DCM, −20° LL 3 h  15  70 DBI 1 mol/[NEt₄]Br₃ 0.3mol/Br₂ 0.3 mol/DCM, rt FL 1 h  11  71 DBI 1 mol/[NEt₄]Br₃ 0.3 mol/Br₂0.3 mol/DCM, rt FL 2 h  25  72 DBI 1 mol/[NEt₄]Br₃ 0.3 mol/Br₂ 0.3mol/DCM, rt FL 4 h  54  73 DBI 1 mol/[NEt₄]Br₃ 0.3 mol/Br₂ 0.3 mol/DCM,rt FL 6 h  83  74 DBI 1 mol/[NEt₄]Br₃ 0.3 mol/DCM, rt FL 1 h  18  75 DBI1 mol/[NEt₄]Br₃ 0.3 mol/DCM, rt FL 4 h  68  76 DBI 1 mol/[NEt₄]Br₃ 0.3mol/DCM, rt FL 6 h  94  77 DBI 1 mol/[N(C₆H₁₃)₄]Br 0.3 mol/Br₂ 0.3mol/DCM, rt FL 1 h  16  78 DBI 1 mol/[N(C₆H₁₃)₄]Br 0.3 mol/Br₂ 0.3mol/DCM, rt FL 4 h  67  79 DBI 1 mol/[N(C₆H₁₃)₄]Br 0.3 mol/Br₂ 0.3mol/DCM, rt FL 6 h  85  80 DBI 1 mol/[BuNEt₃]Br 0.3 mol/Br₂ 0.3 mol/DCM,0° LL 1 h  41  81 DBI 1 mol/[BuNEt₃]Br 0.3 mol/Br₂ 0.3 mol/DCM, 0° LL 2h  77  82 DBI 1 mol/[BuNEt₃]Br 0.3 mol/Br₂ 0.3 mol/DCM, 0° LL 3 h  95 83 DBI 1 mol/[BuNEt₃]Br 0.3 mol/Br₂ 0.3 mol/DCM, 0° LL 4 h 100  84 DBI1 mol/[MeN(C₈H₁₇)₃]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 1 h  9  85 DBI 1mol/[MeN(C₈H₁₇)₃]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 2 h  22  86 DBI 1mol/[MeN(C₈H₁₇)₃]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 4 h  48  87 DBI 1mol/[MeN(C₈H₁₇)₃]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 6 h  72  88 DBI 1mol/[PhNMe₃]Br₃ 0.3 mol/DCM, rt FL 4 h  79  89 DBI 1 mol/[PhCH₂NMe₃]Br₃0.3 mol/DCM, rt FL 1 h  8  90 DBI 1 mol/[PhCH₂NMe₃]Br₃ 0.3 mol/DCM, rtFL 4 h  83  91 DBI 1 mol/[PhCH₂NMe₃]Br₃ 0.3 mol/DCM, rt FL 6 h  89  92DBI 1 mol/[C₅H₅NH]Br₃ 0.3 mol/DCM, rt FL 4 h  76  93 DBI 1 mol/[DBUH]Br₃0.3 mol/DCM, 0° LL 1 h  57  94 DBI 1 mol/[DBUH]Br₃ 0.3 mol/DCM, 0° LL 2h  86  95 DBI 1 mol/[DBUH]Br₃ 0.3 mol/DCM, 0° LL 3 h  94  96 DBI 1mol/[PBu₄]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 1 h  19  97 DBI 1mol/[PBu₄]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 4 h  87  98 DBI 1mol/[PBu₄]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 6 h  81  99

 36 100

 73 101

 95 102

100 103

 40 104

 95 ^(a) All quantities in mole/mole of lauric acid. Water/ice/salt bathtemperatures in degrees Celsius. ^(b) 1-Bromoundecane analyzed by GC.

Example 9 Bromodecarboxylation of Cyclohexanecarboxylic AcidOptimization of the Reaction Conditions

A mixture of cyclohexanecarboxylic acid (0.5 mmol), bromoisocyanurate,additive (optionally) and solvent (4 mL) was stirred under fluorescentroom light irradiation (FL). An aliquot of the reaction mixture washedwith 1 M aq Na₂SO₃, dried over Na₂SO₄, and filtered through shortneutral silica gel pad. The yield of bromocyclohexane was determined bygas chromatography (GC) using 1,2,4,5-tetrachlorobenzene as internalstandard. The results are presented in Table 8.

TABLE 8 Bromodecarboxylation of cyclohexanecarboxylic acid ^(a) entryReaction conditions yield % ^(b) 1 DBI 1 mol/Br₂ 0.2 mol/DCM, rt FL 1 h10 2 DBI 1 mol/Br₂ 0.2 mol/DCM, rt FL 2 h 23 3 DBI 1 mol/Br₂ 0.2mol/DCM, rt FL 3 h 35 4 DBI 1 mol/Br₂ 0.2 mol/DCM, rt FL 4 h 43 5 DBI 1mol/Br₂ 0.3 mol/DCM, rt FL 1 h 23 6 DBI 1 mol/Br₂ 0.3 mol/DCM, rt FL 2 h47 7 DBI 1 mol/Br₂ 0.3 mol/DCM, rt FL 3 h 70 8 DBI 1 mol/Br₂ 0.3mol/DCM, rt FL 4 h 62 9 DBI 1 mol/Br₂ 0.4 mol/DCM, rt FL 1 h 23 10 DBI 1mol/Br₂ 0.4 mol/DCM, rt FL 2 h 49 11 DBI 1 mol/Br₂ 0.4 mol/DCM, rt FL 3h 55 12 DBI 1 mol/Br₂ 0.4 mol/DCM, rt FL 4 h 51 ^(a) All quantities inmole/mole of cyclohexanecarboxylic acid. ^(b) Bromocyclohexane analyzedby GC.

Example 10 Bromodecarboxylation of 2-methylcaproic Acid Optimization ofthe Reaction Conditions

A mixture of 2-methylcaproic acid (0.5 mmol), bromoisocyanurate,additive (optionally) and solvent (4 mL) was stirred under fluorescentroom light irradiation (FL). An aliquot of the reaction mixture washedwith 1 M aq Na₂SO₃, dried over Na₂SO₄, and filtered through shortneutral silica gel pad. The yield of 2-bromohexane was determined by gaschromatography (GC) using 1,2,4,5-tetrachlorobenzene as internalstandard. The results are presented in Table 9.

TABLE 9 Bromodecarboxylation of 2-methylcaproic acid ^(a) entry Reactionconditions yield % ^(b) 1 DBI 1 mol/[NBu₄]Br₃ 0.1 mol/DCM, rt FL 1 h 102 DBI 1 mol/[NBu₄]Br₃ 0.1 mol/DCM, rt FL 3 h 34 3 DBI 1 mol/[NBu₄]Br₃0.1 mol/DCM, rt FL 5 h 59 4 DBI 1 mol/[NBu₄]Br₃ 0.1 mol/DCM, rt FL 19 h72 5 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 1 h 19 6 DBI 1 mol/[NBu₄]Br₃0.3 mol/DCM, rt FL 3 h 59 7 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 5 h79 8 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 7 h 73 9 DBI 1 mol/[NBu₄]Br₃0.5 mol/DCM, rt FL 1 h 33 10 DBI 1 mol/[NBu₄]Br₃ 0.5 mol/DCM, rt FL 2 h67 11 DBI 1 mol/[NBu₄]Br₃ 0.5 mol/DCM, rt FL 3 h 87 12 DBI 1mol/[NBu₄]Br₃ 0.5 mol/DCM, rt FL 4 h 85 13 DBI 1 mol/[NBu₄]Br₃ 0.7mol/DCM, rt FL 1 h 33 14 DBI 1 mol/[NBu₄]Br₃ 0.7 mol/DCM, rt FL 3 h 8815 DBI 1 mol/[NBu₄]Br₃ 0.7 mol/DCM, rt FL 4 h 86 ^(a) All quantities inmole/mole of 2-methylcaproic acid. ^(b) 2-Bromohexane analyzed by GC.

Example 11 Bromodecarboxylation of 4-Chlorophenylacetic AcidOptimization of the Reaction Conditions

A mixture of 4-chlorophenylacetic acid ArCH₂CO₂H (Ar=4-ClC₆H₄) (1 mmol),bromoisocyanurate, additive (optionally) and solvent (6 mL) was stirredunder fluorescent room light irradiation (FL). An aliquot of thereaction mixture was washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, andfiltered through short neutral silica gel pad. The yields of4-chlorobenzyl bromide ArCH₂Br and 4-chlorobenzal bromide ArCHBr₂ weredetermined by gas chromatography (GC) using 1,2,4-trichlorobenzene asinternal standard. The results are presented in Table 10.

TABLE 10 Bromodecarboxylation of 4-chlorophenylacetic acid ArCH₂CO₂H (Ar= 4-ClC₆H₄)^(a) GC yield, % ArCH₂Br/ entry Reaction conditions ArCHBr₂ 1DBI 1 mol/Br₂ 0.3 mol/DCM, FL rt 0.5 h  8:5 2 DBI 1 mol/Br₂ 0.3 mol/DCM,FL rt 1 h  7:13 3 DBI 1 mol/Br₂ 0.3 mol/DCM, FL rt 2 h  4:23 4 DBI 1mol/[NBu₄]Br 0.5 mol/DCM, FL rt 1 h 36:0 5 DBI 1 mol/[NBu₄]Br 0.5mol/DCM, FL rt 2 h 66:0 6 DBI 1 mol/[NBu₄]Br 0.5 mol/DCM, FL rt 3 h 67:07 DBI 1 mol/[NBu₄]Br 0.5 mol/DCM, FL rt 22 h 53:0 8 DBI 1 mol/[NBu₄]Br0.5 mol/Br₂ 0.5 mol/DCM, 82:0 FL rt 1 h 9 DBI 1 mol/[NBu₄]Br 0.5 mol/Br₂0.5 mol/DCM, 83:1 FL rt 2 h 10 DBI 1 mol/[NBu₄]Br₃ 0.5 mol/DCM, FL rt 1h 92:0 11 DBI 1 mol/[NBu₄]Br₃ 0.5 mol/DCM, FL rt 2 h 92:1 12 DBI 1mol/[NBu₄]Br₃ 0.5 mol/DCM, FL rt 3 days 68:8 13 DBI 1 mol/[NBu₄]Br₃ 0.3mol/DCM, FL rt 1 h 95:0 14 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, FL rt 2 h94:2 15 DBI 1 mol/[NBu₄]Br₃ 0.2 mol/DCM, FL rt 1 h 79:0 16 DBI 1mol/[NBu₄]Br₃ 0.2 mol/DCM, FL rt 2 h 93:2 17 DBI 1 mol/[NBu₄]Br₃ 0.1mol/DCM, FL rt 1 h 59:0 18 DBI 1 mol/[NBu₄]Br₃ 0.1 mol/DCM, FL rt 2 h91:1 19 DBI 1 mol/[NBu₄]Br₃ 0.1 mol/DCM, FL rt 3 h 87:3 20 DBI 1mol/[NBu₄]Br₃ 0.05 mol/DCM, FL rt 2 h 78:1 21 DBI 1 mol/[NBu₄]Br₃ 0.05mol/DCM, FL rt 3 h 84:2 21 DBI 1 mol/[NBu₄]Br₃ 0.05 mol/DCM, FL rt 4 h81:4 ^(a)All quantities in mole/mole of 4-chlorophenylacetic acid.

Example 12 Bromodecarboxylation of Alkanoic Acids

A mixture of alkanoic acid RCO₂H (2 mmol), bromoisocyanurate, additive(optionally) and solvent (12 mL) was stirred under fluorescent roomlight irradiation (FL). The reaction mixture washed with 1 M aq Na₂SO₃,dried over Na₂SO₄, filtered through short silica gel pad andconcentrated in vacuo to yield crude alkyl bromide RBr. Optionally, thecrude bromide was purified by chromatography on silica gel. The resultsare presented in Table 11.

TABLE 11 Bromodecarboxylation of alkanoic acids RCO₂H ^(a) yield, %entry RCO₂H Reaction conditions RBr  1 H(CH₂)₁₁CO₂H DBI 1 mol/Br₂ 0.3mol/DCM, 84 rt FL 4 h  2 H(CH₂)₁₁CO₂H DBI 1 mol/[NBu₄]Br₃ 0.1 mol/ 95^(b) DCM, rt FL 5 h  3 c-C₆H₁₁(CH₂)₂CO₂H DBI 1 mol/[NBu₄]Br₃ 0.3 mol/89 DCM, rt FL 4 h  4 Br(CH₂)₁₀CO₂H DBI 1 mol/Br₂ 0.3 mol/DCM, 85 rt FL 4h  5 MeO₂C(CH₂)₆CO₂H DBI 1 mol/Br₂ 0.3 mol/DCM, 83 rt FL 4 h  64-ClC₆H₄CO(CH₂)₂CO₂H DBI 1 mol/Br₂ 0.3 mol/DCM, 99 rt FL 4 h  7PhCO(CH₂)₃CO₂H DBI 1 mol/[NBu₄]Br₃ 0.1 mol/ 69 DCM, rt FL 5 h  8PhCO(CH₂)₄CO₂H DBI 1 mol/[NBu₄]Br₃ 0.3 mol/ 84 DCM, rt FL 4 h  9PhCH₂CO₂H DBI 1 mol/[NBu₄]Br₃ 0.1 mol/ 90 DCM, rt FL 2 h 104-ClC₆H₄CH₂CO₂H DBI 1 mol/[NBu₄]Br₃ 0.1 mol/ 97 DCM, rt FL 2 h 114-PhC₆H₄CH₂CO₂H DBI 1 mol/[NBu₄]Br₃ 0.1 mol/ 82 DCM, rt FL 2 h 12PhCHMeCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 87 DCM, rt FL 3 h 13H(CH₂)₄CHMeCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/  97^(b) DCM, rt FL 3 h 14H(CH₂)₁₆CHMeCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 92 DCM, rt FL 4 h 15Et₂C(CO₂Et)CO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 85 DCM, rt FL 4 h 16c-C₄H₉CO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/  96^(b) DCM, rt FL 3 h 17c-C₆H₁₁CO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/  80^(b) DCM, rt FL 3 h 18c-C₅H₁₁CH(CO₂H)₂ DBI 2 mol/[NBu₄]Br₃ 1 mol/ 25 DCM, rt FL 3 h (55^(b))19 H(CH₂)₁₀CHBrCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 60 DCM, rt FL 3 h 20PhCHClCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 80 DCM, rt FL 3 h 21H(CH₂)₆CHClCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 68 DCM, rt FL 3 h 22EtO₂C(CH₂)₄CHClCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 70 DCM, rt FL 3 h 23PhCHFCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 73 DCM, rt FL 3 h 24H(CH₂)₁₂CHFCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 76 DCM, rt FL 3 h 25EtO₂C(CH₂)₄)CHFCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 64 DCM, rt FL 3 h 26H(CH₂)₄CF(CO₂Et)CO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 73 DCM, rt FL 4 h 27

DBI 1 mol/[NBu₄]Br₃ 0.3 mol/ DCM, rt FL 4 h 68 28

DBI 1 mol/Br₂ 0.3 mol/DCM, rt FL 4 h 61 29

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 4 h 80 30

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 2 h 52 31

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 3 h  60^(c) 32

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 3 h  90^(d) 33

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 4 h 38 34

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 4 h 86 35

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 4 h 90 36

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 4 h 72 37

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 3 h 26 38

DBI 1 mol/[NBu₄]Br₃ 0.3 mol/ DCM, rt FL 4 h 76 39

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 3 h 26 40

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 3 h 82 41 CH₂BrCHBr(CH₂)₅CO₂HDBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 77 DCM, rt FL 4 h 42

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 3 h 67 ^(a) All quantities inmole/mole of alkanoic acid. ^(b)Yield determined by GC. ^(c)Mixture of1.4:1 trans/cis bromides (¹H NMR) ^(d)Mixture of 2:1 exo/endo bromides(¹H NMR)

Entry 1: 1-Bromoundecane ¹H NMR: δ 3.38 (t, J=7 Hz, 2H), 1.84 (m, 2H),1.40 (m, 2H), 1.27 (s, 14H), 0.87 (t, J=7 Hz, 3H) ppm; ¹³C NMR: δ 33.9,33.0, 32.0, 29.71, 29.69, 29.59, 29.5, 28.9, 28.3, 22.8, 14.2 ppm.

Entry 3: (2-Bromoethyl)cyclohexane ¹H NMR: δ 3.24 (t, J=7 Hz, 2H),1.61-1.79 (m, 7H), 1.40-1.52 (m, 3H), 0.85-0.98 (m, 2H) ppm; ¹³C NMR: δ40.4, 36.3, 32.7, 31.8, 26.5, 26.1 ppm.

Entry 4: 1,10-Dibromodecane ¹H NMR: δ 3.39 (t, J=7 Hz, 4H), 1.84 (m,4H), 1.41 (m, 4H), 1.29 (s, 8H) ppm; ¹³C NMR: δ 34.0, 32.8, 29.3, 28.7,28.1 ppm.

Entry 5: Methyl 7-bromoheptanoate ¹H NMR: δ 3.66 (s, 3H), 3.40 (t, J=7Hz, 2H), 2.31 (t, J=7 Hz, 2H), 1.86 (m, 2H), 1.64 (m, 2H), 1.45 (m, 2H),1.37 (m, 2H) ppm; ¹³C NMR: δ 173.9, 51.4, 33.8, 33.7, 32.5, 28.2, 27.7,24.6 ppm.

Entry 6: 3-Bromo-1-(4-chlorophenyl)propan-1-one ¹H NMR: δ 7.89 (d, J=9Hz, 2H), 7.44 (d, J=9 Hz, 2H), 3.73 (t, J=7 Hz, 2H), 3.55 (t, J=7 Hz,2H) ppm; ¹³C NMR: δ 195.7, 139.9, 134.5, 129.4, 129.0, 41.4, 25.6 ppm.

Entry 7: 4-Bromo-1-phenylbutan-1-one ¹H NMR: δ 7.99 (d, J=4 Hz, 2H),7.58 (t, J=7 Hz, 1H), 7.48 (t, J=8 Hz, 2H), 3.56 (t, J=6 Hz, 2H), 3.18(t, J=7 Hz, 2H), 2.30 (quint, J=7 Hz, 2H) ppm; ¹³C NMR: δ 198.5, 136.6,133.1, 128.5, 127.9, 36.4, 33.6, 26.8 ppm.

Entry 8: 5-Bromo-1-phenylpentan-1-one ¹H NMR: δ 7.95 (d, J=7 Hz, 2H),7.56 (t, J=7 Hz, 1H), 7.46 (t, J=7 Hz, 2H), 3.45 (t, J=7 Hz, 2H), 3.01(t, J=7 Hz, 2H), 1.87-2.0 (m, 4H) ppm; ¹³C NMR: δ 199.7, 136.9, 133.2,128.7, 128.1, 37.5, 33.4, 32.3, 22.9 ppm.

Entry 9: Benzyl bromide ¹H NMR: δ 7.46-7.59 (m, 5H), 4.45 (s, 2H) ppm;¹³C NMR δ 137.7, 128.9, 128.6, 128.3, 33.6 ppm.

Entry 10: 4-Chlorobenzyl bromide ¹H NMR: δ 7.33 (s, 4H), 4.47 (s, 2H)ppm; ¹³C NMR: δ 136.3, 134.3, 130.4, 129.0, 32.5 ppm.

Entry 11: 4-Bromomethylbiphenyl ¹H NMR: δ 7.54-7.61 (m, 4H), 7.41-7.48(m, 4H), 7.34-7.39 (m, 1H), 4.52 (s, 2H) ppm; ¹³C NMR: δ 141.3, 140.4,136.8, 129.5, 128.8, 127.6, 127.5, 127.1, 33.5 ppm.

Entry 12: (1-Bromoethyl)benzene ¹H NMR: δ 7.27-7.46 (m, 5H), 5.22 (q,J=7 Hz, 1H), 2.05 (d, J=7 Hz, 3H) ppm; ¹³C NMR: δ 143.3, 128.7, 128.4,126.9, 49.6, 26.9 ppm.

Entry 14: 2-Bromooctadecane ¹H NMR: δ 4.12 (m, 1H), 1.75-1.89 (m, 2H),1.71 (d, J=7 Hz, 2H), 1.40-1.58 (m, 3H), 1.28 (m, 26H), 0.9 (t, J=7 Hz,3H) ppm; ¹³C NMR: δ 51.5, 41.4, 32.1, 29.88, 29.85, 29.82, 29.76, 29.67,29.55, 29.2, 27.9, 26.6, 22.8, 14.2 ppm.

Entry 15: Ethyl 2-bromo-2-ethylbutyrate ¹H NMR: 4.21 (q, J=7 Hz, 2H),2.09 (m, 4H), 1.27 (t, J=7 Hz, 3H), 0.95 (t, J=7 Hz, 6H) ppm; ¹³C NMR170.9, 70.1, 62.0, 32.7, 14.1, 10.1 ppm.

Entry 18: (Dibromomethyl)cyclopentane ¹H NMR: δ 5.70 (d, J=6 Hz, 2H),2.60-2.77 (m, 1H), 1.86-1.96 (m, 2H), 1.40-1.78 (6H) ppm; ¹³C NMR: δ52.6, 52.5, 31.6, 26.0 ppm.

Entry 19: 1,1-Dibromoundecane ¹H NMR: δ 5.7 (t, J=6 Hz, 1H), 2.39 (m,2H), 1.48-1.58 (m, 2H), 1.27 (m, 14H), 0.88 (t, J=7 Hz, 3H) ppm; ¹³CNMR: δ 46.4, 45.6, 32.0, 29.7, 29.6, 29.5, 29.5, 28.4, 28.2, 22.8, 14.2ppm.

Entry 20: (Bromochloromethyl)benzene ¹H NMR: δ 7.56-7.63 (m, 2H),7.33-7.45 (m, 3H), 6.76 (s, 1H) ppm; ¹³C NMR: δ 141.3, 130.0, 128.8,126.3, 57.6 ppm.

Entry 21: 1-Bromo-1-chloroheptane ¹H NMR: δ 5.76 (t, 1H, J=6 Hz, 1H),2.28 (m, 2H), 1.53 (m, 2H), 1.3 (m, 7H), 0.89 (t, J=7 Hz, 3H) ppm; ¹³CNMR: δ 61.1, 44.8, 31.2, 28.2, 27.1, 22.6, 14.1 ppm.

Entry 22: Ethyl 6-bromo-6-chlorohexanoate ¹H NMR: 5.75 (t, J=6 Hz, 1H),4.09 (q, J=7 Hz, 2H), 2.24-2.33 (m, 4H), 1.60-1.70 (m, 2H), 1.51-1.60(m, 2H), 1.20 (t, J=7 Hz, 3H) ppm; ¹³C NMR 173.2, 60.5, 60.4, 53.5,44.2, 34.0, 26.5, 23.8, 14.3 ppm.

Entry 23: (Bromofluoromethyl)benzene ¹H NMR: δ 7.33-7.55 (m, 6H) ppm;13C NMR: δ 138.8 (d, J_(CF)=20 Hz), 130.3, 128.8, 125.2 (d, J_(CF)=6Hz), 92.2 (d, J_(CF)=254 Hz) ppm; ¹⁹F NMR: δ −133.3 ppm.

Entry 24: 1-Bromo-1-fluorotridecane ¹H NMR: δ 6.45 (dt, J=51, 5 Hz, 1H),2.07-2.29 (m, 2H), 1.46-1.56 (m, 2H), 1.27 (m, 19H), 0.88 (t, J=7 Hz,3H) ppm; ¹³C NMR: δ 95.9 (d, J_(CF)=252 Hz), 40.8 (d, J_(CF)=19 Hz),32.0, 29.79, 29.78, 29.73, 29.6, 29.5, 28.8, 25.22, 25.18, 22.8, 14.1ppm; ¹⁹F NMR: −133.3 ppm.

Entry 25: Ethyl 6-bromo-6-fluorohexanoate ¹H NMR: 6.42 (dt, J=50, 5.4Hz, 1H), 4.10 (q, J=7 Hz, 2H), 2.28 (t, J=7 Hz, 2H), 2.00-2.23 (m, 2H),1.60-1.69 (m, 2H), 1.56-1.60 (m, 2H), 1.20 (t, J=7 Hz, 3H) ppm; ¹³C NMR173.2, 95.2 (d, J_(CF)=252 Hz), 60.4, 40.2 (d, J_(CF)=19 Hz), 34.0, 24.6(d, J_(CF)=4 Hz), 24.0, 14.3 ppm; ¹⁹F NMR: δ −134.0 ppm.

Entry 26: Ethyl 2-bromo-2-fluorohexanoate ¹H NMR: 4.34 (q, J=7 Hz, 2H),2.30-2.50 (m, 2H), 1.50-1.65 (2H), 1.31-1.45 (m, 6H), 0.93 (t, J=7 Hz,3H) ppm; ¹³C NMR 166.3 (d, J_(CF)=27 Hz), 98.7 (d, J_(CF)=266 Hz), 63.1,41.4, (d, J_(CF)=21 Hz), 26.4 (d, J_(CF)=1.4 Hz), 22.1, 13.9, 13.8 ppm;¹⁹F NMR: δ −120.1 ppm.

Entry 27: 3α, 7α, 12α-Triformyloxy-5β-23-bromo-24-nor-cholane ¹H NMR: δ8.15 (s, 1H), 8.02 (s, 1H), 8.01 (s, 1H), 5.27 (m, 1H), 5.07 (m, 1H),4.70 (m, 1H), 3.43-3.35 (m, 1H), 3.27-3.38 (m, 1H), 1.02-2.18 (m, 25H),0.94 (s, 3H), 0.85 (d, J=6 Hz, 3H), 0.77 (s, 3H) ppm; ¹³C NMR: δ 160.69,160.68, 160.6, 75.4, 73.9, 70.8, 47.5, 45.3, 43.1, 40.9, 39.0, 37.8,34.6, 34.6, 34.5, 34.4, 34.4, 31.8, 31.5, 28.7, 27.4, 26.7, 25.7, 22.9ppm.

Entry 28: N-(5-Bromopentyl)phthalimide ¹H NMR: δ 7.80 (dd, J=5, 3 Hz,2H), 7.70 (dd, J=5, 3 Hz, 2H), 3.68 (t, J=7 Hz, 2H), 3.38 (t, J=7 Hz,2H), 1.89 (m, 2H), 1.70 (m, 2H), 1.49 (m, 2H) ppm; ¹³C NMR: δ 168.3,133.9, 132.0, 37.6, 33.4, 32.2, 27.7, 25.3 ppm.

Entry 29: Ethyl 1-bromocyclobutanoate ¹H NMR: δ 4.19 (q, J=7 Hz, 2H),2.80-2.90 (m, 2H), 2.50-2.60 (m, 2H), 2.10-2.20 (m, 1H), 1.76-1.87 (m,1H), 1.25 (t, J=7 Hz, 3H) ppm; ¹³C NMR: δ 171.5, 61.9, 54.3, 37.2, 16.7,13.9 ppm.

Entry 30: Methyl 4-bromocubanecarboxylate ¹H NMR: δ 4.22-.4.35 (m, 6H),3.70 (s, 3H) ppm; ¹³C NMR: δ 172.0, 63.3, 56.4, 54.7, 51.8, 47.9 ppm.

Entry 31: trans-1-Bromo-2-(4-chlorobenzoyl)cyclohexane ¹H NMR: δ 7.93(d, J=9 Hz, 2H), 7.46 (d, J=9 Hz, 2H), 4.41 (m, 1H), 3.76 (m, 1H), 2.49(m, 1H), 1.91-2.00 (m, 2H), 1.79-1.89 (m, 2H), 1.37-1.50 (m, 3H) ppm;¹³C NMR: δ 200.0, 140.0, 134.7, 130.0, 129.2, 54.1, 51.4, 37.5, 31.9,27.0, 24.9 ppm.

Entry 32: endo-2-Bromonorbornane ¹H NMR: δ 4.27-4.33 (m, 1H) ppm; ¹³CNMR: δ 54.1, 43.5, 41.6, 37.7, 37.17, 29.6, 24.5 ppm.

Entry 32: exo-2-Bromonorbornane ¹H NMR: δ 3.96-4.02 (m, 1H) ppm; ¹³CNMR: δ 54.1, 46.6, 44.0, 37.2, 35.6, 28.2, 27.7 ppm.

Entry 33: (1S)-1-Bromoapocamphan-2-one ¹H NMR: δ 2.52 (m, 1H), 1.93-2.27(m, 5H), 1.50 (m, 1H), 1.08 (s, 3H), 0.95 (s, 3H) ppm; ¹³C NMR: δ 209.0,77.1, 49.1, 42.5, 40.7, 32.8, 28.1, 20.1, 19.6 ppm.

Entry 34: 1-(Bromomethyl)adamantine ¹H NMR: δ 3.13 (s, 2H), 1.98 (m,3H), 1.69 (d, J=12 Hz, 3H), 1.62 (d, J=12 Hz, 3H), 1.54 (m, 6H) ppm; ¹³CNMR: δ 48.4, 40.7, 36.8, 33.6, 28.5 ppm.

Entry 35: 1-Bromoadamantane ¹H NMR: δ 2.37 (d, J=3 Hz, 6H), 2.1 (m, 3H),1.73 (m, 6H) ppm; ¹³C NMR: δ 49.4, 35.6, 32.6 ppm.

Entry 36: 3-Bromonoradamantane ¹H NMR: δ 2.65 (t, J=7 Hz, 1H), 2.16-2.30(m, 6H), 1.95-2.05 (m, 2H), 1.43-1.63 (m, 4H) ppm; ¹³C NMR: δ 66.1,55.4, 48.8, 43.4, 38.5, 33.4 ppm.

Entry 37: 1-Boc-3-bromoazetidine ¹H NMR: δ 4.49 (m, 3H), 4.16 (m, 2H),1.42 (s, 9H) ppm; ¹³C NMR: δ 155.8, 80.3, 60.3, 33.0, 28.4 ppm.

Entry 38: 1-Boc-4-(bromomethyl)piperidine ¹H NMR: δ 4.13 (m, 1H), 3.29(d, J=6 Hz, 2H), 2.69 (m, 2H), 1.78-1.85 (m, 3H), 1.46 (s, 9H),1.10-1.23 (m, 2H) ppm; ¹³C NMR: δ 154.8, 79.5, 43.6, 38.9, 38.7, 30.9,28.5 ppm.

Entry 39: 1-Boc-4-bromopiperidine ¹H NMR: δ 4.30 (m, 1H), 3.60-3.70 (m,2H), 3.24-3.32 (m, 2H), 2.00-2.10 (m, 2H), 1.85-1.95 (m, 2H), 1.43 (s,9H) ppm; ¹³C NMR: δ 154.7, 79.9, 49.6, 42.2 (bs), 35.7, 28.5 ppm.

Entry 40: 4-Bromo-1-(methylsulfonyl)piperidine ¹H NMR: δ 4.43 (m, 1H),3.37 (m, 4H), 2.80 (s, 3H), 2.16-2.28 (m, 2H), 2.05-2.14 (m, 2H) ppm;¹³C NMR: δ 48.2, 43.2, 35.0, 34.7 ppm.

Entry 41: 1,2,7-Tribromoheptane ¹H NMR: δ 4.17 (m, 1H), 3.86 (dd, J=10,4 Hz, 1H), 3.62 (t, J=10 Hz, 1H), 3.42 (t, J=7 Hz, 1H), 2.11-2.21 (m,1H), 1.75-1.94 (m, 3H), 1.41-1.67 (m, 5H) ppm; ¹³C: δ 52.8, 36.3, 35.9,33.7, 32.6, 27.5, 26.1 ppm.

Entry 42: N-(6-Bromo-6-fluorohexyl)phthalimide ¹H NMR: δ 7.83-7.86 (m,2H), 7.70-7.73 (m, 2H), 6.44 (dt, J=50, 5 Hz, 1H), 3.70 (t, 2H),2.08-2.28 (m, 2H), 1.71 (m, 2H), 1.51-1.61 (m, 3H), 1.36-1.46 (m, 2H)ppm; ¹³C NMR: δ 168.4, 133.9, 132.1, 123.1, 95.4 (d, J_(CF)=252 Hz),40.7 (d, J_(CF)=41 Hz), 37.7, 28.3, 25.9, 24.6, 24.56 ppm; ¹⁹F NMR: δ−133.8 ppm.

Example 13 Bromodecarboxylation of Lauric Acid: Solvent Selection

A mixture of lauric acid (0.5 mmol), DBI (0.5 mmol), [NBu₄]Br₃ (0.15mmol), and solvent (4 mL) was stirred under fluorescent room lightirradiation (FL) or warm-white 3 W LED lamp irradiation (LL). An aliquotof the reaction mixture washed with 1 M aq Na₂SO₃, dried over Na₂SO₄,and filtered through short neutral silica gel pad. The yield of1-bromoundecane was determined by gas chromatography (GC) using1,2,4,5-tetrachlorobenzene as internal standard. The results arepresented in Table 12.

TABLE 12 Bromodecarboxylation of lauric acid ^(a) entry Reactionconditions yield, % ^(b) 1 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 4 h 982 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCE, rt FL 4 h 55 3 DBI 1 mol/[NBu₄]Br₃0.3 mol/CHCl₃, rt FL 4 h 73 4 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/CCl₄, rt FL 4h 6 5 DBI 1 mol/Br₂ 1 mol/DCM, rt FL 1 h 43 6 DBI 1 mol/Br₂ 1 mol/DCM,rt FL 2 h 73 7 DBI 1 mol/Br₂ 1 mol/DCM, rt FL 3 h 70 8 DBI 1 mol/Br₂ 1mol/DCM, rt FL 4 h 60 9 DBI 1 mol/Br₂ 1 mol/CCl₄, rt FL 1 h 11 10 DBI 1mol/Br₂ 1 mol/CCl₄, rt FL 2 h 27 11 DBI 1 mol/Br₂ 1 mol/CCl₄, rt FL 18 h20 12 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/C₆H₆, rt FL 4 h 77 13 DBI 1mol/[NBu₄]Br₃ 0.3 mol/PhCl, rt FL 4 h 73 14 DBI 1 mol/[NBu₄]Br₃ 0.3mol/MeCN, rt FL 4 h 29 15 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/MeOAc, rt LL 1 h44 16 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/MeOAc, rt LL 2 h 53 17 DBI 1mol/[NBu₄]Br₃ 0.3 mol/MeOAc, rt LL 3 h 53 18 DBI 1 mol/[NBu₄]Br₃ 0.3mol/EtOAc, rt LL 1 h 60 19 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/EtOAc, rt LL 2 h68 20 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/EtOAc, rt LL 4 h 68 ^(a) Allquantities in mole/mole of lauric acid. ^(b) 1-Bromoundecane analyzed byGC.

Example 14 Bromodecarboxylation of Lauric Acid: N-Bromoamide Selection

A mixture of lauric acid (0.5 mmol), N-bromoamide (0.5 mmol), [NBu₄]Br₃(0.15 mmol), and DCM (4 mL) was stirred under fluorescent room lightirradiation (FL) or warm-white 3 W LED lamp irradiation (LL). An aliquotof the reaction mixture washed with 1 M aq Na₂SO₃, dried over Na₂SO₄,and filtered through short neutral silica gel pad. The yield of1-bromoundecane was determined by gas chromatography (GC) using1,2,4,5-tetrachlorobenzene as internal standard. The results arepresented in Table 13.

TABLE 13 N-Bromoamides as reagents for radical bromodecarboxylation ^(a)entry Reaction conditions yield, % ^(b) DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM,rt FL 4 h 98 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 20 h 71 NBS 1mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 4 h 1 NBS 1 mol/[NBu₄]Br₃ 0.3 mol/DCM,rt FL 20 h 2 NBSsac 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 4 h 1 DBDMH 1mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 4 h 4 DBDMH 1 mol/[NBu₄]Br₃ 0.3mol/DCM, rt FL 20 h 10 BTH 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 4 h 2 BTH1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 20 h 5 ^(a) All quantities inmole/mole of lauric acid. ^(b) 1-Bromoundecane analyzed by GC.

Example 15 Bromodecarboxylation of Lauric Acid: Recovery of OniumCompound

A mixture of lauric acid (3.13 g, 15.7 mmol), dibromoisocyanuric acidDBI (4.50 g, 15.7 mmol), tetrapropylammonium tribromide [NPr₄]Br₃ (2.00g, 4.7 mmol) and DCM (45 mL) was stirred under warm-white 3 W LED lampirradiation (LL) for 7 h at 0° C. The mixture was filtered and thefiltrate was washed with 1M aq Na₂SO₃ (6.3 mL, 6.3 mmol) and water (20mL), dried over Na₂SO₄, filtered and concentrated in vacuo to give1-bromoundecane (3.56 g, 97% yield).

The combined aqueous phases were treated with Br₂ (1.01 g, 6.3 mmol),washed with DCM (2×60 mL). DCM fraction was dried over Na₂SO₄, filteredand concentrated in vacuo giving g (1.36 g, 68% recovery) of [NPr₄]Br₃.

Example 16 Bromodecarboxylation of Lauric Acid with Bromoisocyanurate A:Preparation of Bromoisocyanurate

The mixture of trichloroisocyanuric acid TCCA (10.0 g, 43.1 mmol), Br₂(41.9 g, 262 mmol) and DCM (50 mL) was stirred at rt in the dark for 18h. The precipitate was filtered off, washed on the filter with DCM andtreated with Br₂ (41.9 g, 262 mmol) in DCM (50 mL) at rt in the dark for18 h. The precipitate was filtered off, washed on the filter with DCMand dried in vacuo giving 14.1 g of bromoisocyanurate.

B: Bromodecarboxylation of Lauric Acid with Bromoisocyanurate

A mixture of lauric acid (0.28 g, 1.4 mmol), bromoisocyanurate from stepA (0.39 g), tetrapropylammonium tribromide [NPr₄]Br₃ (0.58 g, 1.4 mmol),and DCM (4 mL) was stirred at 0° C. under 3 W warm-white LED lampirradiation (LL) for 5 h. The mixture was washed with 1 M aq Na₂SO₃,dried over Na₂SO₄, filtered and concentrated in vacuo. The residue waspurified by chromatography on silica to yield 0.30 g (90%) of1-bromoundecane.

While certain features of the invention have been illustrated anddescribed herein, many modifications, substitutions, changes, andequivalents will now occur to those of ordinary skill in the art. It is,therefore, to be understood that the appended claims are intended tocover all such modifications and changes as fall within the true spiritof the invention.

What is claimed is:
 1. A process for the preparation of organic bromideof formula (1A) from a carboxylic acid of formula (2A) represented byscheme 1:

said process comprises radical bromodecarboxylation reaction ofcarboxylic acid (2A) with a bromoisocyanurate to yield organic bromide(1A); wherein said bromoisocyanurate is tribromoisocyanuric acid,dibromoisocyanuric acid, bromodichloroisocyanuric acid,dibromochloroisocyanuric acid, bromochloroisocyanuric acid, or anycombination thereof; A is arene, alkane, cycloalkane or saturatedheterocycle; n is an integer of at least 1; m is an integer of at least0; and each Q is independently F, Cl, Br, R¹, acyl, C(O)R¹, C(O)OR¹,C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl,OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R¹,N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any twovicinal Q substituents are joined to form a 5- or 6-membered substitutedor unsubstituted, saturated or unsaturated carbocyclic or heterocyclicring; wherein each R¹ is independently aryl, alkyl, cycloalkyl orheterocyclyl, wherein said R¹ is optionally substituted by one or moresubstituents of R²; wherein each R² is independently F, Cl, Br, COOH,acyl, aryl, alkyl, cycloalkyl or heterocyclyl; wherein if either one ofR² in (2A) is carboxylic group COOH, then the respective R² in (1A) isBr; wherein the position of said Br and Q in said structure of formula(1A) correspond to the same position of said COOH and Q, respectively insaid structure of formula (2A).
 2. (canceled)
 3. The process of claim 1,wherein A is benzene.
 4. The process of claim 1, wherein said organicbromide is bromoarene of formula (1B):

and said carboxylic acid is arenecarboxylic acid of formula (2B)

wherein Q¹, Q², Q³, Q⁴, and Q⁵, are each independently selected from: H,F, Cl, Br, R¹, COOH, acyl, C(O)R¹, acetyl, benzoyl, C(O)OR¹, C(O)Cl,C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹,OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R², N(R¹)SO₂R¹,N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two of Q¹ and Q², Q²and Q³, Q³ and Q⁴, or Q⁴ and Q⁵, are joined to form a 5- or 6-memberedsubstituted or unsubstituted, saturated or unsaturated carbocyclic orheterocyclic ring; wherein each R¹ is independently aryl, alkyl,cycloalkyl or heterocyclyl; wherein R¹ is optionally substituted by oneor more substituents of R²; wherein each R² is independently F, Cl, Br,COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl; wherein if eitherone of Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (2B) is carboxylic group COOH,then the respective Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (1B) is Br.
 5. Theprocess of claim 4, wherein at least one of Q¹, Q², Q³, Q⁴, and/or Q⁵ isF, Cl, Br, CF₃, CCl₃, CN, COOH, C(O)OMe, NO₂, OCF₃, and/or any two of Q¹and Q², Q² and Q³, Q³ and Q⁴, or Q⁴ and Q⁵, are joined to form adihydrofuran-2,5-dione or pyrrolidine-2,5-dione ring.
 6. The process ofclaim 1, wherein the molar ratio of bromoisocyanurate/(each carboxylicgroup of the carboxylic acid of formula (2A)) is between 0.1 and
 2. 7.The process of claim 1, wherein said bromodecarboxylation reactionfurther comprises an additive.
 8. The process of claim 7, wherein saidadditive is Br₂ (bromine), a salt comprising bromide or polybromideanion and organic or inorganic cation; or any combination thereof. 9.The process of claim 8, wherein said polybromide anion is an ion offormula[Br_(p)]^(q−) where p is an integer of at least 3 and q is an integer ofat least 1 and not more than p/2.
 10. The process of claim 8, whereinsaid cation is substituted or unsubstituted onium ion.
 11. The processof claim 10, wherein said onium ion comprises substituted orunsubstituted ammonium, oxonium, phosphonium, sulfonium, arsonium,selenonium, telluronium, iodonium ion or any combination thereof. 12.The process of claim 11, wherein said ammonium ion is tertiary orquaternary ammonium, substituted or unsubstituted pyridinium, amidiniumor guanidinium ion; or any combination thereof; or said phosphonium ionis quaternary phosphonium ion; or said sulfonium ion is tertiarysulfonium, substituted; or unsubstituted sulfoxonium, thiopyrylium orthiuronium ion; or any combination thereof; or said oxonium ion istertiary oxonium, substituted or unsubstituted pyrylium ion; or anycombination thereof. 13-16. (canceled)
 17. The process of claim 7,wherein the molar ratio of the additive/(each carboxylic group of thecarboxylic acid of formula (2A)) is between 0.1 and
 4. 18. The processof claim 1, wherein said bromodecarboxylation reaction further comprisesan organic or inorganic solvent or combination thereof.
 19. The processof claim 18, wherein said organic solvent is CH₃CN, CH₃NO₂, ester, ahydrocarbon solvent, or halocarbon solvent or combination thereof. 20.The process of claim 19, wherein said hydrocarbon solvent is C₆H₆; andsaid halocarbon solvent is CH₂Cl₂, Cl(CH₂)₂Cl, CHCl₃, CCl₄, C₆H₅Cl,o-C₆H₄Cl₂, BrCCl₃, CH₂Br₂, CFCl₃, CF₃CCl₃, ClCF₂CFCl₂, BrCF₂CFClBr,CF₃CClBr₂, CF₃CHBrCl, C₆H₅F, C₆H₅CF₃, 4-ClC₆H₄CF₃, 2,4-Cl₂C₆H₃CF₃, orany combination thereof. 21-23. (canceled)
 24. The process of claim 1,wherein in order to accelerate the radical bromodecarboxylation reactionthe reaction mixture is subjected to electromagnetic irradiation. 25-27.(canceled)
 28. The process of claim 1, wherein said bromodecarboxylationreaction further comprises a radical initiator.
 29. The process of claim28, wherein said radical initiator is an azo compound or organicperoxide.
 30. The process of claim 29, wherein said azo compound isazobisisobutyronitrile (AIBN) or 1,1′-azobis(cyclohexanecarbonitrile)(ABCN).
 31. The process of claim 29, wherein said organic peroxide isbenzoyl peroxide.
 32. A radiation-sensitive composition comprisingcarboxylic acid of formula (2A)

and bromoisocyanurate which generates organic bromide of formula (1A)

upon electromagnetic irradiation, wherein the bromoisocyanurate istribromoisocyanuric acid, dibromoisocyanuric acid,bromodichloroisocyanuric acid, dibromochloroisocyanuric acid,bromochloroisocyanuric acid, or any combination thereof; A is arene,alkane, cycloalkane or saturated heterocycle; n is an integer of atleast 1; m is an integer of at least 0; each Q is independently F, Cl,Br, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)OMe, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹,SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl,SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R¹, N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹,N[C(O)R¹]₂, CF₃; or any two vicinal Q substituents are joined to form a5- or 6-membered substituted or unsubstituted, saturated or unsaturatedcarbocyclic or heterocyclic ring; wherein each R¹ is independently aryl,alkyl, cycloalkyl or heterocyclyl, wherein R¹ is optionally substitutedby one or more substituents of R²; wherein each R² is independently F,Cl, Br, COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl; wherein ifeither one of R² in (2A) is a carboxylic group COOH, then the respectiveR² in (1A) is Br; wherein the position of said Br and Q in saidstructure of formula (1A) correspond to the same position of said COOHand Q, respectively in said structure of formula (2A).
 33. (canceled)34. The composition of claim 32, wherein A is benzene.
 35. Thecomposition of claim 32, wherein said carboxylic acid is arenecarboxylicacid of formula (2B)

and said organic bromide is bromoarene of formula (1B)

wherein Q¹, Q², Q³, Q⁴, and Q⁵, are each independently selected from: H,F, Cl, Br, R¹, COOH, acyl, C(O)R¹, C(O)OR¹, C(O)Cl, C(O)N(R¹)₂, CN,SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹,S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R², N(R¹)SO₂R¹, N(acyl)₂,N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two of Q¹ and Q², Q² and Q³, Q³and Q⁴, or Q⁴ and Q⁵, are joined to form a 5- or 6-membered substitutedor unsubstituted, saturated or unsaturated carbocyclic or heterocyclicring; wherein each R¹ is independently aryl, alkyl, cycloalkyl orheterocyclyl wherein R¹ is optionally substituted by one or moresubstituents of R²; wherein each R² is independently F, Cl, Br, COOH,acyl, aryl, alkyl, cycloalkyl or heterocyclyl; wherein if either one ofQ¹, Q², Q³, Q⁴, Q⁵, and/or R² in (2B) is carboxylic group COOH, then therespective Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (1B) is Br.
 36. Thecomposition of claim 35, wherein at least one of Q¹, Q², Q³, Q⁴, and/orQ⁵ is F, Cl, Br, CF₃, CCl₃, CN, COOH, C(O)OMe, NO₂, OCF₃, and/or any twoof Q¹ and Q², Q² and Q³, Q³ and Q⁴, or Q⁴ and Q⁵, are joined to form adihydrofuran-2,5-dione or pyrrolidine-2,5-dione ring.
 37. Thecomposition of claim 32, wherein the molar ratio ofbromoisocyanurate/(each carboxylic group of the carboxylic acid offormula (2A)) is between 0.1 and
 2. 38. The composition of claim 32,which further comprises an additive.
 39. The composition of claim 38,wherein said additive is Br₂ (bromine), a salt containing bromide orpolybromide anion and organic or inorganic cation; or any combinationthereof.
 40. The composition of claim 39, wherein said polybromide anionis an ion of formula[Br_(p)]^(q−) where p is an integer of at least 3 and q is an integer ofat least 1 and no more than p/2.
 41. The composition of claim 39,wherein said cation is substituted or unsubstituted onium ion.
 42. Thecomposition of claim 41, wherein said onium ion comprises substituted orunsubstituted ammonium, oxonium, phosphonium, sulfonium, arsonium,selenonium, telluronium, iodonium ion or any combination thereof. 43.The composition of claim 42, wherein said ammonium ion is tertiary orquaternary ammonium, substituted or unsubstituted pyridinium, amidiniumor guanidinium ion; or any combination thereof; or wherein saidphosphonium ion is quaternary phosphonium ion; or wherein said sulfoniumion is tertiary sulfonium, substituted or unsubstituted sulfoxonium,thiopyrylium or thiuronium ion; or any combination thereof; or whereinsaid oxonium ion is tertiary oxonium, substituted or unsubstitutedpyrylium ion.
 44. The composition of claim 43, wherein said quaternaryammonium is tetraalkylammonium, trialkylarylammonium, ortrialkylbenzylammonium.
 45. The composition of claim 38, wherein themolar ratio of the additive/(each carboxylic group of the carboxylicacid of formula (2A)) is between 0.1 and 4
 46. The composition of claim32, which further comprises of an organic or inorganic solvent orcombination thereof.
 47. The composition of claim 46, wherein saidorganic solvent is CH₃CN, CH₃NO₂, ester, a hydrocarbon solvent, orhalocarbon solvent or combination thereof.
 48. The composition of claim47, wherein said hydrocarbon solvent is C₆H₆; and said halocarbonsolvent is CH₂Cl₂, Cl(CH₂)₂Cl, CHCl₃, CCl₄, C₆H₅Cl, o-C₆H₄Cl₂, BrCCl₃,CH₂Br₂, CFCl₃, CF₃CCl₃, ClCF₂CFCl₂, BrCF₂CFClBr, CF₃CClBr₂, CF₃CHBrCl,C₆H₅F, C₆H₅CF₃, 4-ClC₆H₄CF₃, 2,4-Cl₂C₆H₃CF₃, or any combination thereof.49-54. (canceled)
 55. A composition comprising an organic bromide offormula (1A)

wherein said organic bromide of formula (1A) is prepared by the processaccording to claim 1; wherein A is arene, alkane, cycloalkane orsaturated heterocycle; n is an integer of at least 1; m is an integer ofat least 0; each Q is independently F, Cl, Br, R¹, acyl, C(O)R¹,C(O)OR¹, C(O)OMe, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺,OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl,N(R¹)C(O)R¹, N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; orany two vicinal Q substituents are joined to form a 5- or 6-memberedsubstituted or unsubstituted, saturated or unsaturated carbocyclic orheterocyclic ring; wherein each R¹ is independently aryl, alkyl,cycloalkyl or heterocyclyl, wherein R¹ is optionally substituted by oneor more substituents of R²; wherein each R² is independently F, Cl, Br,COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl; wherein if eitherone of R² in (2A) is a carboxylic group COOH, then the respective R² in(1A) is Br; wherein the position of said Br and Q in said structure offormula (1A) correspond to the same position of said COOH and Q,respectively in said structure of formula (2A).